Ephedrine

1.13

log Kow = 1.13

1.13

Waxy solid, crystals or granules

White to colorless granules, pieces, or crystals

Plates from water

63600

In water, 56,900 mg/L at 25 °C ; 63,600 mg/L at 30 °C

Soluble in oils

Soluble in water, ethanol, ether, benzene and chloroform

1 g dissolves in about 20 mL water, 0.2 mL alcohol

63.6 mg/mL at 30 °C

255

260 °C at 745 mm Hg

Boiling point = 255 °C (decomposes)

34

38.1 °C

34 °C

Mol wt: 201.69. Fine, white, colorless crystals or powder, affected by light, mp 217-220 °C. Odorless. Specific optical rotation: -33 to -35.5 deg ar 25 °C/D ( c = 5). Freely soluble in water, soluble in alcohol. Practically insoluble in ether. /Ephedrine hydrochloride/

Mol wt: 428.55. Fine, white, odorless crystals or powder. Darkens on exposure to light, mp 245 °C (decomposes). Specific optical rotation: -30 to -32.5 deg ar 25 °C/D ( c = 5). Freely soluble in water; sparingly soluble in alcohol. /Ephedrine sulfate/

Specific optical rotation: -6.3 at 20 °C/D (alcohol)

GRADUALLY DECOMP ON EXPOSURE TO LIGHT

AFFECTED BY LIGHT /L-FORM HYDROCHLORIDE, L-FORM SULFATE/

9.61

9.65

10.3 (at 0 °C)

pKa = 9.65 at 25 °C

pKa = 10.25 at 0 °C

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Danger

List I Chemical: A chemical specified by regulation that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act and is important to the manufacture of a controlled substance. (21 eCFR 1310.02)

Status: Active Update: 05-08-2015 https://echa.europa.eu/registration-dossier/-/registered-dossier/11605

Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended or suggested in the labeling, or if no conditions of use are recommended or suggested in the labeling, under ordinary conditions of use. Therefore, dietary supplements containing ephedrine alkaloids are adulterated under section 402(f)(1)(A) of the Federal Food, Drug, and Cosmetic Act.

On February 11, 2004, FDA issued a final regulation declaring dietary supplements containing ephedrine alkaloids adulterated under section 402(f)(1)(A) of the Act. FDA took this action because it found that ephedrine alkaloids present an unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling, or if no conditions of use are suggested or recommended in labeling, under ordinary conditions of use. The final rule became effective on April 12, 2004.

On Aug. 17, 2006, the U.S. Court of Appeals for the Tenth Circuit in Denver upheld the Food and Drug Administration's (FDA) final rule declaring all dietary supplements containing ephedrine alkaloids adulterated, and therefore illegal for marketing in the United States, reversing a decision by the District Court of Utah /made in 2005/.

Although synthetic ephedrine (in the form of ephedrine hydrochloride) has been found in products labeled as dietary supplements, ephedrine hydrochloride was approved for use as a human drug as early as the late 1940s and, to the best of /the FDA's/ knowledge there is no evidence that it was marketed prior to that time as a dietary supplement or food. Furthermore, ephedrine hydrochloride and other synthetic sources of ephedrine cannot be dietary ingredients because they are not constituents or extracts of a botanical, nor do they qualify as any other type of dietary ingredient. For these reasons, products containing synthetic ephedrine cannot be legally marketed as dietary supplements

International Programme on Chemical Safety; Poisons Information Monograph: Ephedrine (PIM 209) (2000) This report contains a discussion of the pharmacological and toxicological effects of ephedrine.[Available from, as of March 21, 2014: http://www.inchem.org/documents/pims/pharm/pim209.htm]

CANTOX; Safety Assessment and Determination of a Tolerable Upper Limit for Ephedra, p. 194 (2000). This very thorough analysis of the information available on ephedra up to 2000 was prepared by CANTOX Health Sciences International, Ontario, for the Council for Responsible Nutrition, Washington, DC, a Washington-based trade association representing ingredient suppliers and manufacturers in the dietary supplement industry.[Available from, as of March 21, 2014: http://www.crnusa.org/pdfs/Cantoxreport.doc]

DHHS/NTP; Toxicology & Carcinogenesis Studies of Ephedrine sulfate in F344/N Rats and B6C3F1 Mice; Technical Report Series No. 307 (1986) NIH Publication No. 86-2563; U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709[Available from, as of March 21, 2014: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr307.pdf]

Thurn AL; p. 189-95 in Encyclopedia of Dietary Supplements; Coates PM et al, eds (2005); A review of Ephedra (Ma Huang)

Between 1995 and 1997, the FDA received more than 900 reports of possible ephedra toxicity. Serious adverse events such as stroke, heart attack, and sudden death were reported in 37 cases.

In 2004, the FDA banned the U.S. sale of dietary supplements containing ephedra. The FDA found that these supplements had an unreasonable risk of injury or illness-particularly cardiovascular complications-and a risk of death. The ban does not apply to traditional Chinese herbal remedies or to products like herbal teas regulated as conventional foods.

In July 2003, GAO /US Government Accountability Office/ testified at a House Subcommittee hearing on issues relating to dietary supplements containing ephedrine alkaloids. ... The testimony ... /included/ an evaluation of Metabolife International's records of health-related calls from consumers of Metabolife 356 /a popular weight-loss supplement containing ma-huang, caffeine, and several other active ingredients./. GAO noted that the types of adverse events identified in the health-related call records from Metabolife International were consistent with the types of adverse events reported to /FDA/, as well as with the scientifically documented physiological effects of ephedrine alkaloids. GAO also noted that despite the limited information contained in most of the call records, 14,684 call records contained reports of at least one adverse event among consumers of Metabolife 356. The GAO testimony identified 92 serious events that included heart attacks, strokes, seizures, and deaths and emphasized that these findings were similar to other reviews of the call records, including those done by Metabolife International and its consultants. The GAO testimony noted that, in those call records where age was documented, many of the serious adverse events occurred in relatively young consumers, with more than one-third being under the age of 30. Furthermore, for those call records in which quantity of use and/or frequency and duration of use were noted, most of the serious adverse events occurred among Metabolife 356 users who used the product within the recommended guidelines, i.e., they did not take more of the product nor consume it for a longer period of time than the product label recommended. /Metabolife 356/

Acute Tox. 4 (100%)；Skin Corr. 1B (52%)；Skin Sens. 1B (52%)；Eye Dam. 1 (52%)

Acute toxicity - category 4

Acute toxicity (Oral) - Category 4；Reproductive toxicity - Category 1A, Additional category: Effects on or via lactation；Specific target organ toxicity - Single exposure - Category 2 (heart, nervous system)；Specific target organ toxicity - Repeated exposure - Category 2 (heart, nervous system)

Acute Tox. 4 *

...must be stored in light-resistant containers. Ephedrine base should be stored at or below 8 °C.

KEEP WELL CLOSED IN COOL PLACE.

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

...A /previously/ healthy 40-year-old man was admitted to our hospital for new-onset congestive heart failure and severe acute hepatitis that developed several months after he began using anabolic-androgenic steroids, ephedra, and gamma-hydroxybutyrate supplements. Analysis with an objective causality assessment scale revealed a probable adverse drug reaction between the patient's use of anabolic steroids, ephedra, and gamma-hydroxybutyrate and the development of his cardiomyopathy and acute liver injury. /Ephedra/

Single-dose studies of dietary supplements containing ephedrine alkaloids show that these products cause increases in both heart rate and blood pressure in healthy subjects. In one such study ... the peak increase in blood pressure following a single oral dose of ephedrine alkaloids and caffeine (20 mg/200 mg) was 14 millimeters of mercury (mm Hg) systolic and 6 mm Hg diastolic, occurring about 2 hours after the single dose was taken. The findings ... are complicated by the presence of caffeine in the dietary supplements used because caffeine is also known to have acute effects on blood pressure and heart rate. /Ephedrine alkaloids/

A group of healthy subjects received ephedrine (E, 0.1 mg/kilogram (kg) orally), caffeine (C, 4 mg/kg orally), the combination, or a placebo (P). Although caffeine caused a small increase in systolic blood pressure (average 3 to 6 mm Hg), ephedrine alone gave a 12 mm Hg effect, and when added to caffeine, increased systolic blood pressure by an additional 15 mm Hg (C+E = 156 +/- 29 mm Hg; E = 150 +/- 14; C = 141 +/ - 16; P = 138 +/- 14).

Serious adverse health events have been reported with the use of dietary supplements containing ephedra and guarana. /The authors/ sought to determine whether repeated dosing and multi-ingredient formulations contribute to the adverse effects of these supplements. ... In this study, 16 healthy adults (8 women) took 2 doses each of ephedra-guarana alone, Xenadrine RFA, a multicomponent dietary supplement containing 25 mg ephedra alkaloids and 200 mg caffeine, or placebo 5 hours apart in a randomized, double-blind, 3-arm crossover study. Peak plasma ephedrine levels averaged 130 to 140 ng/mL. Compared with placebo, Xenadrine and ephedra-guarana significantly increased heart rate (maximum increase, 9.4 +/- 8.6 beats/min; P = 0 .002), blood pressure (maximum increase in systolic and diastolic pressure, 11.5 +/- 10.7 mm Hg and 7.3 +/- 7.4 mm Hg, respectively; P = 0 .015), postprandial glucose concentration (maximum change, 41.0 +/- 18.8 mg/dL; P < .0001), and insulin concentration (maximum change, 41.2 +/- 47.8 microIU/mL; P = .005). Serum potassium concentrations were significantly decreased by both treatments. Hemodynamic and metabolic changes were observed after both the first and second doses. However, plasma free fatty acid concentrations increased after the first dose only. Xenadrine RFA produced higher increases in glucose concentration than ephedra-guarana, but no other pharmacodynamic differences between the treatments were found. /The authors concluded that/ consumption of 2 doses of ephedra and guarana supplements, per supplement label recommendations, results in persistent increases in heart rate and blood pressure and unfavorable actions on glucose and potassium homeostasis. Such effects could be detrimental in persons with hypertension, atherosclerosis, or glucose intolerance, conditions that are strongly associated with obesity.

For more Interactions (Complete) data for (L)-EPHEDRINE (25 total), please visit the HSDB record page.

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergi

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 72(SRC), determined from a structure estimation method(2), indicates that (L)-ephedrine is expected to have high mobility in soil(SRC). The pKa of (L)-ephedrine is 9.65(3), indicating that this compound will exist primarily in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of (L)-ephedrine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.7X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(2). (L)-Ephedrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). (L)-Ephedrine is reported to gradually decomposes on exposure to light(5); therefore, (L)-ephedrine may be susceptible to direct photolysis on soil surfaces exposed to sunlight(SRC). (L)-Ephedrine has been classified as readily biodegradable by sewage sludge following acclimation(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 72(SRC), determined from a structure estimation method(2), indicates that (L)-ephedrine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 8.7X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 1.4(SRC), from its log Kow of 1.13(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). The rate constant for the reaction of hydroxyl radicals in aqueous solutions at pH 10.5 is 2.3X10+9 L/mol-sec(6); this corresponds to an aquatic half-life of 349 days at an aquatic concentration of 1X10-17 hydroxyl radicals per liter(7). (L)-Ephedrine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). (L)-Ephedrine is reported to decompose gradually on exposure to light(8); therefore, (L)-ephedrine may be susceptible to direct photolysis in natural waters exposed to sunlight(SRC). (L)-Ephedrine has been classified as readily biodegradable by sewage sludge following acclimation(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), (L)-ephedrine, which has an estimated vapor pressure of 1.2X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist solely as a vapor in the ambient atmosphere. Since(L)-ephedrine exists as a solid below its melting point of 38.1 °C(3), occurrence in the particulate-phase may be possible(SRC). Vapor-phase (L)-ephedrine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 4 hours(SRC), calculated from its rate constant of 1.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). (L)-Ephedrine is reported to decompose gradually on exposure to light(3); therefore, (L)-ephedrine may be susceptible to direct photolysis by sunlight(SRC).

Ephedrine may produce palpitations, headache, dizziness, nausea, vomiting, restlessness, and anxiety in the conscious patient. Ephedrine is also arrhythmogenic, and clinicians should be cautious when administering patients predisposed to arrhythmias or taking other arrhythmogenic medications, particularly digitalis. When used long-term, the catecholamine excess can result in contraction band necrosis of the myocardium, which predisposes the heart to ventricular arrhythmias.；Another common effect of ephedrine is an alteration in the time until the onset and duration of action of other drugs. This effect is most notable during induction when giving ephedrine to a hypotensive patient before rocuronium.；Additionally, ephedrine may be hepatotoxic, but there seems to be unclear evidence. This idea stems from case reports where ephedra species containing several compounds resulted in liver damage instead of a direct correlation.；A less common effect experienced mostly by illicit users of ephedrine and its derivatives is the development of radiolucent urological ephedrine-containing stones and paranoid schizophrenia.；Drug-Drug Interactions；* Augmentation of the blood pressure: Clonidine, oxytocin, and propofol can increase blood pressure when administered with ephedrine.；* Interactions that antagonize the pressor effect: α-adrenergic antagonists, β-adrenergic antagonists, and reserpine can antagonize the vasopressor effect of ephedrine.；* Guanethidine: Ephedrine may inhibit the neuron blockage induced by guanethidine, resulting in loss of antihypertensive efficacy.；* Rocuronium: Ephedrine may decrease the onset time of neuromuscular blockade when used with rocuronium for intubation if administered simultaneously. No interventions are needed.；* Theophylline: Concomitant use of ephedrine and theophylline may increase nervousness and insomnia.；* Cardiac glycosides: Administering ephedrine with a cardiac glycoside, such as digitalis, may increase the likelihood of arrhythmias. Monitor patients on digoxin who are administered ephedrine.

IDENTIFICATION: Ephedrine is a colorless or white solid powder or crystals. It has a bitter taste and is odorless or slight aromatic odor. It is soluble in water, alcohol, chloroform, ether, glycerol, olive oil and in liquid paraffin. Ephedrine and its optical isomer pseudoephedrine are structurally very similar to methamphetamine. In illicit drug laboratories simple dehydrogenation is used to make methamphetamine from ephedrine. Indications: The most important uses are: as a bronchodilator; nasal decongestant; and treatment for syndrome of Stokes-Adams; as a mydriatic and hypertensor in the spinal anesthesia. It is also used as an herbal diet supplement under the name Ma-huang as an anorectic and CNS stimulant. HUMAN EXPOSURE: Contraindications: Cardiovascular disease; hypertension; hyperthyroidism; pheochromocytoma and closed angle glaucoma. Ephedrine should not be given in patients being treated with MAOI (or have stopped treatment in the last 14 days). It should be used with caution in patients with prostatic enlargement or with renal impairment. Routes of exposure: Oral: Abuse of ephedrine-containing diet pills is a common occurrence. Inhalation: Ephedrine salts are used as nasal drops or sprays in the relief of nasal congestion associated with cold or rhinitis. Ephedrine can be abused by the nasal route by subjects who have developed dependence to its vasoconstrictive effect. Dermal: As an ointment is well absorbed. Eye: Eye-drops at 0.1% are effective in congestion of conjunctival allergy. Parenteral: Subcutaneous or intramuscular injections. Kinetics: Absorption by route of exposure: Ephedrine is readily and completely absorbed from the gastrointestinal tract; plasma peak concentrations are reached an hour after ingestion. Biological half-life by route of exposure: It has a plasma half-life ranging from 3 to 6 hours depending on urinary pH. No change in half-life from that seen with therapeutic dosing was observed in an otherwise healthy patient wi

According to the manufacturer's prescribing information, an overdose of ephedrine can cause a rapid rise in blood pressure. In the case of an overdose, careful blood pressure monitoring is recommended. If blood pressure rises to an unacceptable level, parenteral antihypertensive agents can be administered at the clinician's discretion.；Signs and Symptoms: The principal manifestation of ephedrine poisoning is hypertension and convulsions. A case report of cardiomyopathy and spinal artery vasospasm leading to quadriplegia has been noted.；Treatment: If respirations are shallow or cyanosis is present, secure the airway and provide mechanical ventilation.；Antidote: For hypertension, 5 mg phentolamine mesylate diluted in saline may be administered slowly intravenously, or clinicians may give 100 mg orally. Convulsions may be controlled by benzodiazepines.

Ephedrine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

(L)-Ephedrine occurrence in plants(1).[Table#4381]

Ephedrine occurrence in plants(1). /Ephedrine/[Table#4382]

Side-effects can include sweating, dry mouth, blurred vision, insomnia, loss of appetite, and dizziness. In addition users can feel restless, anxious and moody, become excitable and have a false sense of power and security. Amphetamine overdose can also cause cardiac arrhythmias, headaches, convulsions, hypertension, rapid heart rate, coma and death. Amphetamines are psychologically and physically addictive.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of March 19, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=299-42-3]

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Ephedrine sulfate/[Available from, as of March 19, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=134-72-5]

List I Chemical: A chemical specified by regulation that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act and is important to the manufacture of a controlled substance. (21 eCFR 1310.02)

Status: Active Update: 05-08-2015 https://echa.europa.eu/registration-dossier/-/registered-dossier/11605

Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended or suggested in the labeling, or if no conditions of use are recommended or suggested in the labeling, under ordinary conditions of use. Therefore, dietary supplements containing ephedrine alkaloids are adulterated under section 402(f)(1)(A) of the Federal Food, Drug, and Cosmetic Act.

On February 11, 2004, FDA issued a final regulation declaring dietary supplements containing ephedrine alkaloids adulterated under section 402(f)(1)(A) of the Act. FDA took this action because it found that ephedrine alkaloids present an unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling, or if no conditions of use are suggested or recommended in labeling, under ordinary conditions of use. The final rule became effective on April 12, 2004.

On Aug. 17, 2006, the U.S. Court of Appeals for the Tenth Circuit in Denver upheld the Food and Drug Administration's (FDA) final rule declaring all dietary supplements containing ephedrine alkaloids adulterated, and therefore illegal for marketing in the United States, reversing a decision by the District Court of Utah /made in 2005/.

Although synthetic ephedrine (in the form of ephedrine hydrochloride) has been found in products labeled as dietary supplements, ephedrine hydrochloride was approved for use as a human drug as early as the late 1940s and, to the best of /the FDA's/ knowledge there is no evidence that it was marketed prior to that time as a dietary supplement or food. Furthermore, ephedrine hydrochloride and other synthetic sources of ephedrine cannot be dietary ingredients because they are not constituents or extracts of a botanical, nor do they qualify as any other type of dietary ingredient. For these reasons, products containing synthetic ephedrine cannot be legally marketed as dietary supplements

C01CA26

C - Cardiovascular system；C01 - Cardiac therapy；C01C - Cardiac stimulants excl. cardiac glycosides；C01CA - Adrenergic and dopaminergic agents；C01CA26 - Ephedrine

R - Respiratory system；R01 - Nasal preparations；R01A - Decongestants and other nasal preparations for topical use；R01AA - Sympathomimetics, plain；R01AA03 - Ephedrine

R - Respiratory system；R03 - Drugs for obstructive airway diseases；R03C - Adrenergics for systemic use；R03CA - Alpha- and beta-adrenoreceptor agonists；R03CA02 - Ephedrine

R - Respiratory system；R01 - Nasal preparations；R01A - Decongestants and other nasal preparations for topical use；R01AB - Sympathomimetics, combinations excl. corticosteroids；R01AB05 - Ephedrine

S - Sensory organs；S01 - Ophthalmologicals；S01F - Mydriatics and cycloplegics；S01FB - Sympathomimetics excl. antiglaucoma preparations；S01FB02 - Ephedrine

Ephedrine increases blood pressure by stimulating heart rate and cardiac output and variably increasing peripheral resistance. It causes bronchodilation due to the activation of beta-adrenergic receptors in the lungs. By stimulating alpha-adrenergic receptors in bladder smooth muscle cells, ephedrine also increases the resistance to the outflow of urine. The therapeutic window of ephedrine is wide, as patients can be given doses of 5mg up to 50mg. Patients should be counselled regarding the pressor effects of sympathomimetic amines and the risk of tachyphylaxis. Also, the use of ephedrine for hypotension prophylaxis is associated with a higher risk of hypertension, compared to when ephedrine is used to treat hypotension.

Ephedrine is a direct and indirect sympathomimetic amine. As a direct effect, ephedrine activates alpha-adrenergic and beta-adrenergic receptors. As an indirect effect, it inhibits norepinephrine reuptake and increases the release of norepinephrine from vesicles in nerve cells. These actions combined lead to larger quantities of norepinephrine present in the synapse for more extended periods of time, increasing stimulation of the sympathetic nervous system. Ephedrine acts as an agonist of alpha-1, beta-1 and beta-2-adrenergic receptors. The stimulation of alpha-1-adrenergic receptors causes the constriction of veins and a rise in blood pressure, the stimulation of beta-1-adrenergic receptors increases cardiac chronotropy and inotropy, and the stimulation of beta-2-adrenergic receptors causes vasodilation and bronchodilation.

Ephedrine alkaloids are members of a large family of sympathomimetic compounds that include dobutamine and amphetamine. Members of this family increase blood pressure and heart rate by binding to alpha- and beta-adrenergic receptors present in many parts of the body, including the heart and blood vessels. These compounds are called sympathomimetics because they mimic the effects of epinephrine and norepinephrine, which occur naturally in the human body. In addition to their direct pharmacological effects, many of these compounds also stimulate the release of norepinephrine from nerve endings. The release of norepinephrine further increases the sympathomimetic effects of these compounds, at least transiently.

Ephedrine does not contain a catechol moiety, and it is effective after oral administration. The drug stimulates heart rate and cardiac output and variably increases peripheral resistance; as a result, ephedrine usually increases blood pressure. Stimulation of the alpha-adrenergic receptors of smooth muscle cells in the bladder base may increase the resistance to the outflow of urine. Activation of beta-adrenergic receptors in the lungs promotes bronchodilation.

Ephedrine stimulates both alpha- and beta-adrenergic receptors. It is believed that beta-adrenergic effects result from stimulation of the production of cyclic adenosine 3',5'-monophosphate (AMP) by activation of the enzyme adenyl cyclase, whereas a-adrenergic effects result from inhibition of adenyl cyclase activity. In contrast to epinephrine, ephedrine also has an indirect effect by releasing norepinephrine from its storage sites. With prolonged use or if doses are given frequently, ephedrine may deplete norepinephrine stores in sympathetic nerve endings and tachyphylaxis may develop to the cardiac and pressor effects. Tachyphylaxis to the bronchial effects of the drug may also occur, but it is not the result of norepinephrine depletion.

Oral ephedrine has a plasma elimination half life of approximately 6 hours, but there is a large degree of inter-patient variability.

...serum half-life of 2-3 hr.

Ephedrineis eliminated in the urine largely as unchanged drug, with a t1/2 of 3-6 hrs.

Ephedrine is largely unmetabolized in the body. Ephedrine can be N-demethylated to norephedrine, or demethylated and deaminized to benzoic acid conjugates and 1,2-hydroxypropylbenzene.

... After /volunteers (n=3 for each drug) consumed a single clinical dose of ephedrine (EPH), pseudoephedrine (PEPH), phenylpropanolamine (PPA), methylephedrine (MEPH) or cathine/..., urine samples were subjected to tert-butyl-methyl-ether (TBME) extraction and trifluoroacetic acid (TFAA) derivatization before gas chromatography-mass spectrometry (GC-MS) analysis. Most ephedrines were excreted unchanged in urine, including EPH (40.9%), PEPH (72.2%), and PPA (59.3%). However, only a relatively small amount of MEPH (15.5%) was excreted unchanged in urine. In addition, a trace amount of PPA (1.6%) and cathine (0.7%) was found to be the metabolites of EPH and PEPH, respectively. Urinary EPH, PEPH, and PPA reached peaks at 2-6 hr and disappeared in urine at approximately 24-48 hr post-administration. For MEPH, the peaks of excretion extended from 4 to 12 hr post-administration and were undetectable at approximately 48 hr. A single clinical dose of EPH (25 mg) may exceed threshold level (10 ug/mL) in sport drug testing if the urine samples are tested within approximately 8 hr post-administration. However, a single dose of MEPH (20 mg) never reached the threshold value (10 ug/mL).

The metabolism of ephedrine in humans, dogs and several species of rodents proceeds primarily by three reactions; aromatic hydroxylation, N-demethylation, and oxidative deamination. The extent to which ephedrine is metabolized and the major metabolites vary quantitatively between species. The extent of aromatic hydroxylation is greatest in rats, followed by rabbits, guinea pigs, and dogs, with no aromatic hydroxylation observed in humans. N-demethylation of ephedrine is greatest in rabbits followed by dogs, guinea pigs, rats, and humans. Deamination is greatest in rabbits, followed by humans and rats. Ephedrine, 8-20%, is metabolized in humans by N-demethylation to /phenylpropanolamin/ PPA. A total of 4-13% of an oral dose of ephedrine undergoes oxidative deamination yielding 1-phenylpropan-1,2-diol and further side-chain oxidation to benzoic acid and hippuric acid.

Yields L-norephedrine and phenylglycol in rabbits. /from table/

Route of Elimination: mainly renal Half Life: 3-6 hours

GN83C131XS

EPHEDRINE

Established Pharmacologic Class [EPC] - alpha-Adrenergic Agonist

Mechanisms of Action [MoA] - Adrenergic alpha-Agonists

Established Pharmacologic Class [EPC] - beta-Adrenergic Agonist

Mechanisms of Action [MoA] - Adrenergic beta-Agonists

A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.

Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.

Drugs used to cause constriction of the blood vessels.

Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.

Oral ephedrine reaches an average Cmax of 79.5ng/mL, with a Tmax of 1.81h, and a bioavailability of 88%.

Ephedrine is mainly eliminated in the urine. Approximately 60% is eliminated as the unmetabolized parent compound, 13% as benzoic acid conjugates, and 1% as 1,2-dihydroxypropylbenzene.

Oral ephedrine has an average volume of distribution of 215.6L.

Oral ephedrine has a clearance of 23.3L/h but there is a high degree of inter-patient variability.

Placental transfer of ephedrine occurs at 70% of the maternal blood levels. Ephedrine is also excreted in breast milk.

Up to 95% of an oral dose may be excreted in the urine within 24 hours. The urinary excretion of ephedrine is pH-dependent due to the presence of an ionizable group in the ephedrine molecule and is increased in acidic urine. In alkaline urine, excretion is reduced to 20 to 35% of the dose.

In Oriental medicines, ephedra is the chief drug for treatment of asthma and bronchitis. It has been used for thousands of years in traditional Chinese medicine as a primary component of multi-herb formulas prescribed to treat bronchial asthma, cold and flu, cough and wheezing, feven, chills, lact of perspiration, headache, and nasal congestion. ...Today, ephedra is official in the national pharmacopeias of China, Germany, and Japan. In India, ephedra herb is listed in the Ayurvedic pharmacopeia. Only its isolated derivatives ephedrine and ephedrine hydrochloride are official in the Indian Pharmacopeia. /Ephedra/

Ephedra is an evergreen shrub-like plant native to Central Asia and Mongolia. The principal active ingredient, ephedrine, is a compound that can powerfully stimulate the nervous system and heart. Ephedra has been used for more than 5,000 years in China and India to treat conditions such as colds, fever, flu, headaches, asthma, wheezing, and nasal congestion. More recently, ephedra was used as an ingredient in dietary supplements for weight loss, increased energy, and enhanced athletic performance.

In Germany, ephedra is official in the German Pharmacopeia and is an approved herb in the Commission E monographs. It is used as a primary component of licensed prepared respiratory medicines. /Ephedra/

Because of its stimulant effects, ephedrine has been misused and abused by athletes, bodybuilders, weight lifters, and others, including high school- and college-aged individuals engaged in sports. Evidence from several surveys indicates that about 4% of student athletes and 13-25% of individuals attending a gymnasium use ephedrine.

For more Uses (Complete) data for (L)-EPHEDRINE (14 total), please visit the HSDB record page.

Use (kg) in Switzerland (2009): >75；Use (kg; approx.) in Germany (2009): >75；Consumption (g per capita) in Switzerland (2009): 0.0096；Consumption (g per capita; approx.) in Germany (2009): 0.00092；Excretion rate: 0.93；Calculated removal (%): 75.2

(1979) No Data

(1981) No Data

(1979) 1.40X10+9 G-TOTAL FOR FREE BASE & SALTS

(1981) 1.33X10+9 G-TOTAL FOR FREE BASE & SALTS

(1979) MORE THAN 4.54X10+6 G (FREE BASE ONLY)

(1981) MORE THAN 4.54X10+6 G (HCL SALT ONLY)

ESSENTIALLY 100% AS A MEDICINAL (FREE BASE & SALTS, 1981)

The American Herbal Products Association contacted 42 companies known to distribute dietary supplements containing ephedrine alkaloids. The 13 companies that responded reported aggregate figures of 3,086,041,072 servings sold in 1999. /Ephedrine alkaloids/

Fermentation of benzaldehyde & molasses with yeast to give levo-1-phenyl-2-keto-1-propanol which is condensed with methylamine & reduced with activated aluminum in moist ether to yield the free base; the salts are produced by addition of hydrochloric or sulfuric acid

Microbial fermentation medium + benzaldehyde + methylamine (microbial conversion/reductive amination)

Ephedrine is a naturally occurring alkaloid drug derived from Ephedra equistina and Ephedra vulgaris.

(-)-Ephedrine can be obtained from the Ma Huang drug (Ephedra "vulgaris", E. sinica Stapf, E. equisetina Bunge) and other types of Ephedra. The powdered drug is alkalized and extracted with benzene. The solution obtained is extracted with dilute acid, and the ephedrine crystallized after concentration of the aqueous phase.

Ephedrine is obtained be the catalytic hydrogenation of (-)-1-phenyl-2-methlyaminopropan-1-one.

Available as the free base, the hydrochloride and the sulfate salts.

Grade: Technical, NF

The most commonly used herbal ephedra, ma-huang contains total ephedrine alkaloids at 0.5-2.5% by weight; ephedrine accounts for 30-90% of these alkaloids.

Ephedrine, its salts, optical isomers, and salts of optical isomers

A chemical specified by regulation that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act and is important to the manufacture of a controlled substance. (21 eCFR 1310.02)

Benzenemethanol, .alpha.-[(1S)-1-(methylamino)ethyl]-, (.alpha.R)-: ACTIVE

The term ephedra is often used to refer to ephedrine alkaloids from botanical sources, whether or not they are contained in dietary supplements. The term ephedrine is generally used to refer to pharmaceutical or synthetic sources of ephedrine.

Ephedrine contains two asymmetrical carbon atoms; only l-ephedrine and racemic ephedrine are used clinically.

The ephedrine alkaloids... are chemical stimulants that occur naturally in some botanicals, but can be synthetically derived. The ingredient sources of the ephedrine alkaloids in dietary supplements include raw botanicals (i.e., plants) and extracts from botanicals. Ma huang, Ephedra, Chinese Ephedra, and epitonin are several names used for botanical ingredients, primarily from Ephedra sinica Stapf, Ephedra equisetina Bunge, Ephedra intermedia var. tibetica Stapf and Ephedra distachya L. (the Ephedras), that are sources of ephedrine alkaloids. Other plant sources that contain ephedrine alkaloids include Sida cordifolia L. and Pinellia ternata (Thunb.) Makino. Common names that have been used for the various plants that contain ephedrine alkaloids include sea grape, yellow horse, joint fir, popotillo, and country mallow. ... Although the proportions of the various ephedrine alkaloids in botanical species vary from one species to another, in most species used commercially, ephedrine is typically the predominant alkaloid in the raw material.

... There are about 50 known species of Ephedra. The ratio of ephedrine to other alkaloids varies from species to species; all North American species lack alkaloids. ... In the trade and raw drug market, Ephedra is available in the form of stem cuttings or powders, without any vouchers, thus making identification of the species difficult. Using light microscopy ...the presence of Ephedra herb /can be detected/, even in powder form, and ... within certain limits its geographical origin /can be identified/. Identification of Chinese and North American species of Ephedra has been made easier by developing a key using leaf and internode length as key identification characters.

For more General Manufacturing Information (Complete) data for (L)-EPHEDRINE (7 total), please visit the HSDB record page.