벤즈페타민

4.1

4.1

Readily soluble

Practically insol in water; sol in methanol, ethanol, ether, chloroform, acetone, benzene

2.33e-02 g/L

129-130

152 - 153 °C

Odorless; polymorphic with one form melting at about 130 °C & another at about 150 °C & higher with decomposition /Benzphetamine hydrochloride/

Crystals from ethyl acetate. Dextrorotatory; mp: 129-130 °C; sol in water, 95% ethanol. /Benzphetamine hydrochloride/

White to off-white crystalline powder. 1 g soluble in 1.5 mL water, 1.5 mL alcohol, 1.5 mL chloroform. /Benzphetamine hydrochloride/

MW 275.82 /Benzphetamine hydrochloride/

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous sxstem, including its salts, isomers (whether optical, position, or geometric), and salts of such isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: Benzphetamine, Schedule III, DEA Code #: 1228.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl benzphetamine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Benzphetamine Hydrochloride/

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Management of acute amphetamine intoxication is largely symptomatic and includes sedation with a barbiturate. If hypertension is marked, the use of a nitrite or rapidly acting alpha receptor blocking agent should be considered. Acidification of the urine increases amphetamine excretion. (L1712)

Concurrent use /of other CNS stimulation-producing medications or thyroid hormones with appetite suppressants / may increase the CNS stimulant effects of either these medications or the appetite suppressant. /Appetite suppressants, sympathomimetic/

The sympathomimetic effects of appetite suppressants /when used with monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline/ may be potentiated, possibly resulting in a hypertensive crisis; concurrent use is contraindicated; appetite suppressant should not be administered during or within 14 days following the administration of and MAO inhibitor. /Appetite suppressants, sympathomimetic/

Vasopressant effect may be potentiated; if necessary to administer a pressor amine agent to a patient who has recently received an appetite suppressant, initiating pressor therapy in reduced dosage and monitoring blood pressure at frequent intervals are recommended. /Appetite suppressants, sympathomimetic/

Anorectic effects of the appetite suppressant may be antagonized /when used with phenothiazines/. /Appetite suppressants, sympathomimetic/

For more Interactions (Complete) data for BENZPHETAMINE (10 total), please visit the HSDB record page.

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.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8.0X10+4(SRC), determined from a structure estimation method(2), indicates that benzphetamine is expected to be immobile in soil(SRC). The estimated pKa of benzphetamine is 8.8(3), indicating that this compound will primarily exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4). Volatilization of benzphetamine from moist soil surfaces is not expected to be an important environmental fate process(SRC) given an estimated Henry's Law constant of 4.2X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Benzphetamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.0X10-4 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2005).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8.0X10+4(SRC), determined from a structure estimation method(2), indicates that benzphetamine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4.2X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). However, the estimated pKa of benzphetamine is 8.8(5), indicating that this compound will primarily exist in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(6). According to a classification scheme(7), an estimated BCF of 300(SRC), from an estimated log Kow of 3.0(8) and a regression-derived equation(9), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). Biodegradation data were not available(SRC, 2005).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), benzphetamine, which has an estimated vapor pressure of 1.0X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase benzphetamine 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 3.5 hours(SRC), calculated from its rate constant of 1.1X10-14 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase benzphetamine will be removed from the atmosphere by wet and dry deposition. Benzphetamine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION: Benzphetamine is a centrally acting antiobesity agent. Benzphetamine is a clear liquid which is insoluble in water. Soluble in ethanol, methanol, chloroform, acetone, ether or benzene. Benzphetamine hydrochloride is a solid crystalline material. 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. 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. Acute transient ischemic colitis has occurred with chronic methamphetamine abuse. Genitourinary: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur 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 amphetamine 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

Although the mechanism of action of the sympathomimetic appetite suppressants in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Amphetamine and related sympathomimetic medications (such as benzphetamine) are thought to stimulate the release of norepinephrine and/or dopamine from storage sites in nerve terminals in the lateral hypothalamic feeding center, thereby producing a decrease in appetite. This release is mediated by the binding of benzphetamine to centrally located adrenergic receptors.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of benzphetamine can be estimated to be 8.0X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that benzphetamine is expected to be immobile in soil. The estimated pKa of benzphetamine is 8.8(3), indicating that this compound will primarily exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

/SIGNS AND SYMPTOMS/ Acute overdosage with amphetamines may result in restlessness, tremor, tachypnea, confusion, assaultiveness and panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Hyperpyrexia and rhabdomyolysis have been reported and can lead to a number of associated complications. Fatal poisoning is usually preceded by convulsions and coma.

/SIGNS AND SYMPTOMS/ Manifestation of chronic intoxication with anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia. /Benzphetamine hydrochloride/

/SIGNS AND SYMPTOMS/ Palpitation, tachycardia, and increased blood pressure may occur in patients receiving benzphetamine. Pulmonary hypertension and cardiomyopathy, usually manifested as ventricular hypertrophy and/or congestive heart failure, have occurred in patients receiving amphetamines chronically (e.g., chronic abusers) and is potentially fatal; the cardiomyopathy is similar to adrenergic cardiomyopathies (e.g., that associated with pheochromocytoma).

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous sxstem, including its salts, isomers (whether optical, position, or geometric), and salts of such isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: Benzphetamine, Schedule III, DEA Code #: 1228.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl benzphetamine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Benzphetamine Hydrochloride/

Benzphetamine, a phenylalkylamin, is related to amphetamine both chemically and pharmacologically. It is an anorectic agent indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction. Benzphetamine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for.

The mechanism of action of these drugs is not fully understood, however it may be similar to that of amphetamines. Amphetamines stimulate noepinephrine and dopamine release in nerve endings in the lateral hypothalamic feeding centre, decreasing appetite. This release is mediated by the binding of benzphetamine to centrally located adrenergic receptors.

Wt loss ... almost entirely due to reduced food intake & only in small measure to increased metabolism. Site of action is central & is probably in lateral hypothalamic feeding center; injection ... into this area but not into ventromedial satiety center, suppresses food intake. /Amphetamine/

Amphetamine appears to exert most or all of its effects in the CNS by releasing biogenic amines from their storage sites in the nerve terminals. The alerting effect of amphetamine, its anorectic effect, & at least a component of its locomotor-stimulating action are presumably mediated by release of norepinephrine from central noradrenergic neurons. /Amphetamine/

Benzphetamine apparently produces an anorexigenic effect and loss of weight. As with other amphetamine derivatives, no primary effect on appetite has been demonstrated with benzphetamine and it is probable that its anorexigenic effect is secondary to CNS stimulation.

16 to 31 hours

Half-life 6-12 hours.

Hepatic. Benzphetamine's metabolites include amphetamine and methamphetamine.

Benzphetamine yields n-benzyl-n,alpha-dimethylphenethylamine-n-oxide in pigs and n-benzyl-alpha-methylphenylamine in rabbits. /From table/

Recent studies have provided spectral evidence for presence of inhibitory product-cytochrome P450 complexes formed from ... /metabolism of benzphetamine/. ... Complexes ... thought to reduce ... the amount of co-complexing cytochrome and to inhibit metabolism by noncompetitive mechanism.

The following pathway for metabolism of benzphetamine (bz) in rat hepatic microsomes was established: benzphetamine yields norbenzphetamine (norbz), n-hydroxynorbenzphetamine, n-benzylethyl-alpha-phenylnitrone, & 2-nitroso-1-phenylpropane. The latter product forms a complex with cytochrome p450 with an absorbance max at 455 nm. Steps 1, 2, & 4 are cytochrome p450-dependent; step 3 appears to involve the flavoprotein mixed-function amine oxidase. Step 2 is partially uncoupled, producing hydrogen peroxide at approx 3 times the rate of n-hydroxylation. Benzphetamine is oxidized to norbz in microsomes from both untreated rats (u-microsomes) & phenobarbital (pb)-treated rats, but 455-nm peak does not appear in u-microsomes until almost all of the benzphetamine has been converted to norbz, ie, benzphetamine inhibits the oxidation of norbz in u- but not in phenobarbital-microsomes. The inhibition is competitive. Benzphetamine inhibits the oxidation of nitrone to 2-nitroso-a-phenylpropane in both u- & phenobarbital-microsomes; norbz inhibits this reaction in u-microsomes only.

Electrophoretically homogeneous cytochrome p450lm2 isolated from phenobarbital-induced rabbits & p450lm4 isolated from beta-naphthoflavone-induced animals differed in the higher activity of the former toward benzphetamine & p-nitrophenetole.

The reconstituted liver microsomal hydroxylation system was used to study the formation of a metabolite-cytochrome p450 complex absorbing maximally at 455 nm, with benzphetamine.

0M3S43XK27

BENZPHETAMINE

Physiologic Effects [PE] - Appetite Suppression

Physiologic Effects [PE] - Increased Sympathetic Activity

Established Pharmacologic Class [EPC] - Sympathomimetic Amine Anorectic

Benzphetamine is a Sympathomimetic Amine Anorectic. The physiologic effect of benzphetamine is by means of Appetite Suppression and Increased Sympathetic Activity.

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.

Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.

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.

Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.

Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.

Readily absorbed from the gastro-intestinal tract and buccal mucosa. It Is resistant to metabolism by monoamine oxidase.

... Benzphetamine /is/ distributed into breast milk. ...

Benzphetamine is readily absorbed from the gastrointestinal tract.

Benzphetamine is readily absorbed from the GI tract and effects persist for about 4 hours after oral administration.

Appetite suppressant

THERAP CAT: Anorexic

MEDICATION

For the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction

Prepared by benzylating (+)-desoxyephedrine with benzyl chloride in presence of sodium carbonate, the resulting benzphetamine being separated by distillation & then converted to hydrochloride. /Benzphetamine hydrochloride/

Prepared from d-desoxyephedrine: Heinzelman, Aspergren, US 2789138 (1957 to Upjohn)

Benzphetamine can be prepared by treating methamphetamine ... with a benzylhalide in the presence of a base.

... Benzphetamine hydrochloride (didrex), 25- & 50-mg tablets ... /Benzphetamine hydrochloride/

Oral: Tablets 50 mg Didrex (C-III; with povidone, scored), (Pfizer) /Benzphetamine hydrochloride/

SCHEDULE III DRUG.

Controlled substance

Manufactured for Pharmacia & Upjohn Co. A subsidiary of Pharmacia Corp., Kalamazoo, MI 49001, USA. By: Moravia Pharmaceuticals, Manati PR 00674. Revised October, 2003. /Hydrochloride/