펜메트라진

>5 mg/L

2.44e+00 g/L

MELTS WITHIN RANGE OF 3 DEG BETWEEN 172 °C & 182 °C; PKA 7.6 /PHENMETRAZINE HYDROCHLORIDE/

Crystals from ethanol + ether; mp: 182 °C; 1 g dissolves in 0.4 ml water, 2.0 ml 95% alc, 2.0 ml chloroform; sparingly sol in ether /Phenmetrazine hydrochloride/

WHITE TO OFF-WHITE, CRYSTALLINE POWDER /PHENMETRAZINE HYDROCHLORIDE/

Odorless; bitter taste; pH 4.5 to 5.5 (2.5% in water) /Phenmetrazine hydrochloride/

DHHS/NIDA; Research Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability (1984) DHHS Pub No. (ADM)87-1332

DHHS/NIDA; Research Monograph Series 54: Mechanisms of Tolerance and Dependence (1984) DHHS Pub No. (ADM)88-1330

DHHS/NIDA; Research Monograph Series 56: Etiology of Drug Abuse: Implications for Prevention (1987) DHHS Pub No. (ADM)87-1335

DHHS/NIDA; Research Monograph Series 59: Current Research on the Consequences of Maternal Drug Abuse (1985) DHHS Pub No. (ADM)85-1400

For more Special Reports (Complete) data for PHENMETRAZINE (8 total), please visit the HSDB record page.

SRP: At the time of review, 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.

A double blind controlled study in psychiatric patients indicated that chlorpromazine reduced the ability of phenmetrazine to produce a weight loss /mechanism not established/. Another study in 30 obese psychiatric patients yielded similar results. Thus, it does appear that chlorpromazine (and possibly other phenothiazines) can reduce the efficacy of phenmetrazine, such as it is.

Amobarbital (90 mg/day) appeared to inhibit the weight reducing ability of phenmetrazine /mechanism not established/ in 50 patients. The effect of barbiturates on the response to other anorexiants is not established, but may be similar.

Like amphetamines, phenmetrazine may decrease the hypotensive effect of guanethidine. /Phenmetrazine hydrochloride/

Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.

IDENTIFICATION: Phenmetrazine hydrochloride is an antiobesity drug. Indications: Appetite suppressant (anorectic). Misuse: Performance enhancement and relief of fatigue Abuse: Abuse either orally or by injection is extremely common. HUMAN EXPOSURE: Main risks and target organs: Acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Summary of clinical effects: Cardiovascular: Palpitation, chest pain, tachycardia, arrhythmias and hypertension are common; cardiovascular collapse can occur in severe poisoning. Myocardial ischemia, infarction and ventricular dysfunction are described. Central Nervous System (CNS): Stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia are described. Stroke and cerebral vasculitis have been observed. Gastrointestinal: Vomiting, diarrhea and cramps may occur. Genitourinary: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can result secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Dermatologic: Skin is usually pale and diaphoretic, but mucous membranes appear dry. Endocrine: Transient hyperthyroxinemia may be noted. Metabolism: Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Fluid/Electrolyte: Hypo- and hyperkalemia have been reported. Dehydration is common. Musculoskeletal: Fasciculations and rigidity may be noted. Rhabdomyolysis is an important consequence of severe poisoning. Psychiatric: Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Contraindications: Anorexia, insomnia, psychopathic personality disorders, suicidal tendencies, Tourette syndrome and other disorders, hyperthyroidism, narrow angle glaucoma, diabetes mellitis and cardiovascular diseases such as angina, hypertension and arrhythmias. It interacts with several other CNS stimulant drugs. Routes of exposure: Oral: Readily absorbed from the gastro-intestinal tract and buccal mucosa. It is resistant to metabolism by monoamine oxidase. Inhalation: Rapidly absorbed by inhalation and is abused by this route. Absorption by route of exposure: Rapidly absorbed after oral ingestion. Peak plasma levels occur within 1 to 3 hours, varying with the degree of physical activity and the amount of food in the stomach. Absorption is usually complete by 4 to 6 hours. Sustained release preparations are available as resin-bound, rather than soluble, salts. These compounds display reduced peak blood levels compared with standard preparations, but total amount absorbed and time to peak levels remain similar. Distribution by route of exposure: Concentrated in the kidney, lungs, cerebrospinal fluid and brain. They are highly lipid soluble and readily cross the blood-brain barrier. Protein binding and volume of distribution varies widely. Biological half-life by route of exposure: Under normal conditions, about 30% is excreted unchanged in the urine but this excretion is highly variable and is dependent on urinary pH. When the urinary pH is acidic (pH 5.5 to 6.0), elimination is predominantly by urinary excretion with approximately 60% of a dose of being excreted unchanged by the kidney within 48 hours. When the urinary pH is alkaline (pH 7.5 to 8.0), elimination is predominantly by deamination (less than 7% excreted unchanged in the urine); the half-life ranging from 16 to 31 hours. Metabolism: The major metabolic pathway involves deamination by cytochrome P450 to para-hydroxy compound and phenylacetone; this latter compound is subsequently oxidized to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Elimination and excretion: Normally 5 to 30% of a therapeutic dose is excreted unchanged in the urine by 24 hours, but the actual amount of urinary excretion and metabolism is highly pH dependent. Mode of action: It appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especially norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Human data: Adults: The toxic dose varies considerably due to individual variations and the development of tolerance. Children: Children appear to be more susceptible than adults and are less likely to have developed tolerance. Teratogenicity: It generally does not appear to be a human teratogen. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long term sequelae, although more studies of this nature are needed. Illicit maternal use or abuse presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. These poor outcomes are probably multifactorial in origin, involving multiple drug use, life-styles and poor maternal health. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. Interactions: Acetazolamide: administration may increase serum concentration. Alcohol: may increase serum concentration. Ascorbic acid: lowering urinary pH, may enhance excretion. Furazolidone: may induce a hypertensive response in patients taking furazolidone. Guanethidine: inhibits the antihypertensive response to guanethidine. Haloperidol: limited evidence indicates that haloperidol may inhibit the effects but the clinical importance of this interaction is not established. Lithium carbonate: isolated case reports indicate that lithium may inhibit the effects. Monoamine oxidase inhibitor: severe hypertensive reactions have followed the administration to patients taking monoamine oxidase inhibitors. Norepinephrine: amphetamine abuse may enhance the pressor response to norepinephrine. Phenothiazines: may inhibit the antipsychotic effect of phenothiazines, and phenothiazines may inhibit the anorectic effect .Sodium bicarbonate: large doses of sodium bicarbonate inhibit the elimination thus increasing the effect. Tricyclic antidepressants: theoretically increases the effect, but clinical evidence is lacking. Clinical effects: Acute poisoning: Ingestion: Effects are most marked on the central nervous system, cardiovascular system, and muscles. The triad of hyperactivity, hyperpyrexia, and hypertension is characteristic of acute amphetamine overdosage. Agitation, confusion, headache, delirium, and hallucination, can be followed by coma, intracranial hemorrhage, stroke, and death. Chest pain, palpitation, hypertension, tachycardia, atrial and ventricular arrhythmia, and myocardial infarction can occur. Muscle contraction, bruxism (jaw-grinding), trismus (jaw clenching), fasciculation, rhabdomyolysis, are seen leading to renal failure; and flushing, sweating, and hyperpyrexia can all occur. Hyperpyrexia can cause disseminated intravascular coagulation. Inhalation: The clinical effects are similar to those after ingestion, but occur more rapidly. Parenteral exposure: Intravenous injection is a common mode of administration. The euphoria produced is more intense, leading to a rush or flash which is compared to sexual orgasm. Other clinical effects are similar to those observed after ingestion, but occur more rapidly. Chronic poisoning: Ingestion: Tolerance to the euphoric effects and CNS stimulation induced develops rapidly, leading abusers to use larger and larger amounts to attain and sustain the desired affect. Habitual use or chronic abuse usually results in toxic psychosis classically characterized by paranoia, delusions and hallucinations, which are usually visual, tactile or olfactory in nature, in contrast to the typical auditory hallucinations of schizophrenia. The individual may act on the delusions, resulting in bizarre violent behavior, hostility and aggression, sometimes leading to suicidal or homicidal actions. Dyskinesia, compulsive behavior and impaired performance are common in chronic abusers. The chronic abuser presents as a restless, garrulous, tremulous individual who is suspicious and anxious. Course, prognosis, cause of death: Symptoms and signs give a clinical guide to the severity of intoxication as follows: Mild toxicity: restlessness, irritability, insomnia, tremor, hyperreflexia, sweating, dilated pupils, flushing; Moderate toxicity: hyperactivity, confusion, hypertension, tachypnea, tachycardia, mild fever, sweating; Severe toxicity: delirium, mania, self-injury, marked hypertension, tachycardia, arrhythmia, hyperpyrexia, convulsion, coma, circulatory collapse. Death can be due to intracranial hemorrhage, acute heart failure or arrhythmia, hyperpyrexia, rhabdomyolysis and consequent hyperkalemia or renal failure, and to violence related to the psychiatric effects. Systematic description of clinical effects: Cardiovascular: Cardiovascular symptoms of acute poisoning include palpitation and chest pain. Tachycardia and hypertension are common. One third of patients reported had a blood pressure greater than 140/90 mmHg, and nearly two-thirds had a pulse rate above 100 beats per minute. Severe poisoning can cause acute myocardial ischemia, myocardial infarction, and left ventricular failure. These probably result from vasospasm, perhaps at sites of existing atherosclerosis. In at least one case, thrombus was demonstrated initially. Chronic oral abuse can cause a chronic cardiomyopathy; an acute cardiomyopathy has also been described. Hypertensive stroke is a well-recognized complication of poisoning. Intra-arterial injection can cause severe burning pain, vasospasm and gangrene. Respiratory: Pulmonary fibrosis, right ventricular hypertrophy and pulmonary hypertension are frequently found at post-mortem examination. Pulmonary function tests usually are normal except for the carbon monoxide diffusing capacity. Respiratory complications are sometimes caused by fillers or adulterants used in injections by chronic users. These can cause multiple microemboli to the lung, which can lead to restrictive lung disease. Neurological: Central nervous system (CNS): Main symptoms include agitation, confusion, delirium, hallucinations, dizziness, dyskinesia, hyperactivity, muscle fasciculation and rigidity, rigors, tics, tremors, seizures and coma. Both occlusive and hemorrhagic strokes have been reported after abuse. Patients with underlying arteriovenous malformations may be at particular risk. Stroke can occur after oral, intravenous, or nasal administration. Severe headache beginning within minutes of ingestion is usually the first symptom. In more than half the cases, hypertension which is sometimes extreme, accompanies other symptoms. A Cerebral vasculitis has also been observed. Dystonia and dyskinesia can occur, even with therapeutic dosages. Psychiatric effects, particularly euphoria and excitement, are the motives for abuse. Paranoia and a psychiatric syndrome indistinguishable from schizophrenia are sequelae of chronic use. Autonomic nervous system: Stimulation of alpha-adrenergic receptors produces mydriasis, increased metabolic rate, diaphoresis, increased sphincter tone, peripheral vasoconstriction and decreased gastrointestinal motility. Stimulation of ß-adrenergic receptors produces increased heart rate and contractility, increased automaticity and dilatation of bronchioles. Skeletal and smooth muscle: Myalgia, muscle tenderness, muscle contractions, and rhabdomyolysis, leading to fever, circulatory collapse, and myoglobinuric renal failure, can occur. Gastrointestinal: Most common symptoms are nausea, vomiting, diarrhea, and abdominal cramps. Anorexia may be severe. Epigastric pain and hematemesis have been described after intravenous use. Hepatic: Hepatitis and fatal acute hepatic necrosis have been described. Urinary: Renal: Renal failure, secondary to dehydration or rhabdomyolysis may be observed. Other: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. This effect may be a direct result of peripheral alpha-agonist activity. Endocrine and reproductive systems: Transient hyperthyroxinemia may result from heavy use. Dermatological: Skin is usually pale and diaphoretic, but mucous membranes appear dry. Chronic users may display skin lesion, abscesses, ulcers, cellulitis or necrotizing angiitis due to physical insult to skin, or dermatologic signs of dietary deficiencies, such as cheilosis, purpura. Eye, ear, nose, and throat: local effects: Mydriasis may be noted. Diffuse hair loss may be noted. Chronic users may display signs of dietary deficiencies. Hematological: Disseminated intravascular coagulation is an important consequence of severe poisoning. Idiopathic thrombocytopenic purpura may occur. Fluid and electrolyte disturbance: Increase metabolic and muscular activity may result in dehydration. Special risks: Is passed into breast milk and measurable amounts can be detected in breast-fed infant's urine. Therefore lactating mothers are advised not to take or use the drug. /Phenmetrazine hydrochloride/

Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space. Dopamine integrates incoming sensory stimuli, initiates and controls fine movement (nigro-neostriatal pathway), controls emotional behavior (midbrain mesolimbic-forebrain system) and controls hypothalamic-pituitary endocrine system (tubero-infundibular system). It is this latter effect on the tubero-infundibular systm that seems to lead to reduced food intake. Phenmetrazine also acts as a monoamine oxidase inhibitor.

Symptoms of overdose include acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension, and cardiovascular collapse. Whilst some patients show signs of toxicity at blood concentrations of 20 µg/L, chronic abusers of amphetamine have been known to have blood concentration of up to 3000 µg/L.

PHENMETRAZINE (PRELUDIN), AN ANOREXIC, IN OVERDOSAGE HAS CAUSED MYDRIASIS WITH IMPAIRED PUPILLARY RESPONSE TO LIGHT & ACCOMMODATION CONVERGENCE, ASSOCIATED WITH GENERAL PHYSICAL OVERACTIVITY ... ABNORMALITIES OF MOOD, HALLUCINATIONS, & DISORIENTATION, ALL REVERSIBLE. ORDINARY ORAL DOSAGE OF 12.5 TO 50 MG OF PHENMETRAZINE APPEARS TO HAVE LITTLE INFLUENCE ON THE PUPILS. /PHENMETRAZINE HYDROCHLORIDE/

IN AN OBSERVATIONAL STUDY OF PREGNANCY & CHILD DEVELOPMENT, THE PHENMETRAZINE PRESCRIBED DURING DIFFERENT STAGES OF PREGNANCY WAS EVALUATED FOR TERATOGENICITY. THE SEVERE CONGENITAL ANOMALY RATE PER 100 LIVE-BORN CHILDREN AT 5 YR DID NOT DIFFER FROM THE SEVERE CONGENITAL ANOMALY RATE OF THE GROUP OF CHILDREN WHOSE MOTHERS DID NOT USE PHENMETRAZINE.

Marked prostration resembling septic shock, disseminated intravascular coagulation, rhabdomyolysis with myoglobinuria & uremia appeared to be associated with the intravenous abuse of phenmetrazine ... in 5 patients. /Phenmetrazine hydrochloride/

The abuse of this drug involves both oral and intravenous use, most of the abuse involves the injection of tablets dissolved in water. Complication arising ... since the tablets contain insoluble materials, which when injected, block small blood vessels and cause serious damage ... in the lung and retina of the eye.

Morphine sulfate and pentobarbital sodium had no effect on iv cocaine hydrochloride self-administration behavior until the doses of the analgesic and hypnotic were 2.0 mg/kg and 15.0 mg/kg, doses causing a general depression. Morphine sulfate, pentobarbital sodium, cocaine hydrochloride, d-amphetamine sulfate 0.5-4.0 mg/kg and phenmetrazine hydrochloride 2.0-12.0 mg/kg pretreatments produced a dose-dependent decrease in cocaine hydrochloride self-administration. d-Amphetamine sulfate /and/ phenmetrazine hydrochloride, trifluoperazine hydrochloride increased the frequency at 0.01-0.1 mg/kg, but at 0.2-0.4 mg/kg markedly depressed this behavior. Trifluoperazine hydrochloride, imipramine hydrochloride 10-15 mg/kg caused a dose-related decrease in cocaine hydrochloride self-administration. The mechanisms of these drug-behavior and drug-drug interactions are discussed. /Phenmetrazine hydrochloride/

Drug-naive dogs were trained to respond for intravenous infusions of either d-amphetamine, phenmetrazine, or methylphenidate until a stable response rate per 4-hr daily session was achieved. The magnitude of reinforcement (i.e., mg/kg/infusion) was then varied systematically across a wide range for each drug. An inverse relationship between unit dose and number of self-administered infusions per session was seen. Thus, total drug intake per session remained relatively constant and was independent of unit dose. Using a parallel line bioassay design, the relative potencies of d-amphetamine, phenmetrazine, and methylphenidate to maintain self-administration were estimated. By comparing the unit doses of d-amphetamine which yielded the same rate of self-administration it was found that 1 mg of phenmetrazine is equivalent to 0.1 mg of d-amphetamine. It was also determined that 1 mg of methylphenidate is equivalent to 0.75 mg of d-amphetamine. These data indicate the dog can be used to assess the reinforcing properties of psychomotor stimulants.

... The effects of psychoactive drugs on central monoamine neurons of the rat were studied. Fifteen to 30 min before the injection of 250 mg H 44/68 /kg, given 4, 6, or 8 hr prior to killing, rats received one of the following desipramine 25 mg/kg, protriptyline 25 mg/kg, +-amphetamine 10 or 1 mg/kg plus a second dose of 5 or 0.5 mg/kg 3 hr. After the first injection, nialamide 100-250 mg/kg, phenmetrazine 40 mg/kg, or chlordiazepoxide 300 mg/kg. In some rats desipramine at 25 mg/kg, ethanol 2 g/kg, or pentobarbitone at 40 mg/kg plus a second dose of 15 mg/kg 90 min later were given 30 min before the administration of 500 mg alpha-propyldopacetamide/kg, the latter given 3 hr before killing. All drugs were given ip. The antidepresive drugs desipramine, protriptyline, and low doses of +-amphetamine did not influence the rate of noradrenaline and dopamine depletion after tyrosine hydroxylase inhibition. This lack of effect may be because the stimulation of synthesis caused by increase local loss of amine is counteracted by the negative feedback on the presynaptic catechol amine neuron, triggered by the increased amounts of transmitter reaching the adrenergic receptor sites. Large doses of +-amphetamine, on the other hand, increased the rate of amine depletion from the noradrenaline nerve terminals after tyrosine hydroxylase inhibition, whereas nialamide markedly reduced the rate of depletion. /Chlordiazepoxide and phenmetrazine in the relatively high doses used did not influence desipramine and ethanol did not affect the activity of the 5-hydroxytryptamine neurons, whereas pentobarbitone probably decreased their activity./

Following chronic ingestion of phenmetrazine, psychotic manifestations resembling schizophrenia can occur. In rat experiments, phenmetrazine increased the rate of cerebral metabolism leading to substrate deficiency. Psychoses caused by phenmetrazine responded to neuroleptics, such as chlorpromazine or perazine, which had a favorable therapeutic influence on schizophrenic psychoses. When regarding phenmetrazine-induced psychoses as a model of substrate-deficiency disorder which can be compensated by neruoleptics, the question arises whether this model might also be applied to a least some of the real schizophrenic posychoses.

For more Non-Human Toxicity Excerpts (Complete) data for PHENMETRAZINE (6 total), please visit the HSDB record page.

LD50 Rat oral 370 mg/kg

LD50 Mouse oral 125 mg/kg

LD50 Mouse ip 125 mg/kg

LD50 Mouse sc 195 mg/kg

Phenmetrazine is a sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Phenmetrazine was originally sold under the tradename Preludin as an anorectic. It has since been removed from the market. It is by some considered to have a greater potential for addiction than the amphetamines, and has been abused in many countries, for example Sweden.

Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space. Dopamine integrates incoming sensory stimuli, initiates and controls fine movement (nigro-neostriatal pathway), controls emotional behavior (midbrain mesolimbic-forebrain system) and controls hypothalamic-pituitary endocrine system (tubero-infundibular system). It is this latter effect on the tubero-infundibular systm that seems to lead to reduced food intake. Phenmetrazine also acts as a monoamine oxidase inhibitor.

As with other amphetamine derivatives, no primary effect on appetite has been demonstrated with phenmetrazine & it is probable that its anorexigenic effect is secondary to CNS stimulation. /Phenmetrazine hydrochloride/

THEY DECREASE APPETITE BY STIMULATING THE HYPOTHALAMUS TO RELEASE CATECHOLAMINES IN THE CNS. ... ANOREXIANT DRUGS (EXCEPT FENFLURAMINE) INCREASE PHYSICAL ACTIVITY, & ALL OF THESE AGENTS HAVE METABOLIC EFFECTS INVOLVING FAT (INHIBITING LIPOGENESIS, ENHANCING LIPOLYSIS) AND CARBOHYDRATE METABOLISM, BUT THESE PROBABLY ARE SECONDARY TO SUPPRESSION OF APPETITE. /ANOREXIANTS/

The mechanisms of reinforcement are still uncertain /for many drugs/. ... Amphetamine & phenmetrazine appear to release newly synthesized neurotransmitter selectively, & their effects can be blocked by inhibition of tyrosine hydroxylase ...

16 to 31 hours

Following oral admin of a single 75 mg dose as conventional tablets, phenmetrazine has a plasma half life of about 8 hr in healthy adults. /Phenmetrazine hydrochloride/

Primarily hepatic (via CYP3A and CYP2D6). Resistant to metabolism by monoamine oxidase. Metabolism involves deamination to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidize to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation.

In humans, principal urinary metabolites of the drug are lactam derivative & a phenolic hydroxyphenmetrazine derivative & its glucuronide; the drug also is metabolized to a nitrone derivative. /Phenmetrazine hydrochloride/

IN MAN, THE 24 HR METABOLITES OF ORALLY ADMIN PHENMETRAZINE (0.35 MG/KG) WERE 22% FREE & CONJUGATED 3-METHYL-2-(4-HYDROXYPHENYL)MORPHOLINE, 19% FENMETRAMIDE, & 5% UNKNOWN METABOLITE, WITH 19% UNCHANGED PHENMETRAZINE.

Little unchanged 5-methyl-6-phenylmorpholine was excreted in the urine of either rats or guinea pigs, while man excreted approx 1/5 of the dose unchanged & the tamarin monkey 2/5. More detailed analysis of the urine permitted the identification of 4 major metabolites. The phenol /derivative/ & its glucuronide are important in all species except the guinea pig. In this animal 5-methyl-3-oxo-6-phenylmorpholine was the major urinary metabolite. The inability of the guinea pig to ring-hydroxylate amphetamine derivatives is well known. A product of N-oxidation, tentatively identified as phenmetrazine nitrone, was found in appreciable quantities in the urine of the guinea pig & tamarin monkey.

Primarily hepatic (via CYP3A and CYP2D6). Resistant to metabolism by monoamine oxidase. Metabolism involves deamination to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidize to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation. Half Life: 16 to 31 hours

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.

Agents that are used to suppress appetite.

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.

Readily absorbed from the gastro-intestinal tract and buccal mucosa.

Phenmetrazine hydrochloride is readily absorbed from the gastrointestinal tract ... Avg peak concn were obtained about 2 hr after ingestion. /Phenmetrazine hydrochloride/

A single dose of a sustained release prepn (Preludin Endurets) containing phenmetrazine 75 mg yielded blood concn at 8 & 12 hr after ingestion comparable to those obtained with the same dose of phenmetrazine hydrochloride ...

... The drug is excreted in urine principally as metabolites. Although elimination via biliary excretion (about 6% of a dose over 5 days) has been observed in rats, it is unlikely that appreciable biliary excretion occurs in humans. ... About 19% of a dose is excreted unchanged in urine within 24 hr. /Phenmetrazine hydrochloride/

Little unchanged 5-methyl-6-phenylmorpholine was excreted in the urine of either rats or guinea pigs, while man excreted approx 1/5 of the dose unchanged & the tamarin monkey 2/5.

... Phenmetrazine hydrochloride /is/ no longer commercially available in the USA. /Phenmetrazine hydrochloride/

MEDICATION

MEDICATION: VET

Used as an anorectic in the treatment of obesity.

BY CYCLIZING ALPHA-(1-((2-HYDROXYETHYL)AMINO)ETHYL)BENZYL ALC WITH AID OF STRONG SULFURIC ACID OR OTHER SUITABLE DEHYDRANTS. ALC MAY BE SYNTHESIZED THROUGH ADDITION REACTION INVOLVING ETHYLENE OXIDE & ALPHA-(1-AMINOETHYL)BENZYL ALC (NOREPHEDRINE). BASE REACTS READILY WITH EQUIMOLAR QUANTITY OF HYDROCHLORIDE TO FORM THE SALT. /PHENMETRAZINE HYDROCHLORIDE/

Prepn: Thomae, Wick, U.S. patent 2,835,669 (1958 to Boehringer, Ing.); Seimer, Hengen, U.S. patent 3,018,222 (1962 to Ravensberg Cgem.); Clark, J. Org. Chem. 27, 3251 (1962); Klosa, J. Prakt. Chem. 21, 12 (1963).

Phenmetrazine is prepared by reacting alpha-bromopropiophenone with N-benzylethanolamine, catalytic reduction of the intermediate ketone to N-hydroxyethyl norephedrine or norpseudoephedrine, and then cyclization with concentrated sulfuric acid.

... PHENMETRAZINE HYDROCHLORIDE, NF (PRELUDIN), 25-MG TABLETS & 50- & 75-MG SLOW RELEASE TABLETS ...

Marsin, neo-zine /Phenmetrazine hydrochloride/

Preludin: 25 mg tablets; 75 and 105 mg slow-release capsules. /From table/