Chlorphentermine

183.67800

183.68

207-314-9

NHW07912O7

1645

DTXSID0022806

C65323

LIQUID

2921499090

26.02000

3.32010

1.074g/cm3

100-102 °C @ Press: 2 Torr

127ºC

1.537

WHITE TO OFF-WHITE POWDER; ODORLESS & HAS BITTER TASTE; FREELY SOL IN WATER & ALC; SPARINGLY SOL IN CHLOROFORM; PRACTICALLY INSOL IN ETHER /CHLORPHENTERMINE HYDROCHLORIDE/

CRYSTALS FROM ALCOHOL + ETHER; MP: 234 °C; PH OF 1% AQ SOLN: APPROX 5.5; SOL IN WATER: >20% /CHLORPHENTERMINE HYDROCHLORIDE/

IRRITANT

SH1050000

STABLE IN LIGHT & AIR /CHLORPHENTERMINE HYDROCHLORIDE/

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H302

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).|Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule III includes chlorphentermine, DEA Code #1645; Drug class: Stimulant.|Drugs; statement of required warning. The label of any drug listed as a "controlled substance" in schedule II, III, or IV of the Federal Controlled Substances Act shall, when dispensed to or for a patient, contain the following warning: "Caution: Federal law prohibits the transfer of this drug to any person other than the patient for whom it was prescribed." This statement is not required to appear on the label of a controlled substance for use in clinical investigations which are "blind".|The Discontinued Drug Product List identifies discontinued drug products including chlorphentermine hydrochloride (Pre-State, Parke Davis). The Lists contains products that have never been marketed, products discontinued withdrawn for other than safety or effectiveness reasons. /Chlorphentermine hydrochloride/

Reasor MJ; A review of the biology and toxicologic implications of the induction of lysosomal lamellar bodies by drugs.; Toxicol Appl Pharmacol 97 (1): 47-56 (1989). Over 30 drugs of differing pharmacologic action are capable of inducing lamellar bodies of lysosomal origin in cells of animals and humans. The structures develop because of a drug-induced impairment in lysosomal phospholipid catabolism. Toxicity frequently accompanies the induction of these bodies. However, little information exists as to whether their development or presence is causally linked to the cellular or tissue dysfunction. This review examines the biological aspects of the induction of lysosomal lamellar bodies by drugs and considers the toxicologic implications of their presence in cells.

IDENTIFICATION: Chlorphentermine hydrochloride is a centrally acting antiobesity drug. 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 occurs 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 Tourette syndrome and other disorders, hyperthyroidism, narrow angle glaucoma 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, diabetes mellitius and cardiovascular diseases such as angina, hypertension and arrythmias. Routes of exposure: Oral: Readily absorbed from the gastro-intestinal tract and buccal mucosa. It is resistant to metabolism by monoamine oxidase. Inhalation: Amphetamine is rapidly absorbed by inhalation and is often abused by this route. Parenteral: Frequent route of entry in abuse situations. Absorption by route of exposure: Amphetamine is 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 amphetamine preparations, but total amount absorbed and time to peak levels remain similar. Distribution by route of exposure: Amphetamines are concentrated in the kidney, lungs, cerebrospinal fluid and brain. They are highly lipid soluble and readily cross the blood-brain barrier. Biological half-life by route of exposure: Under normal conditions, about 30% of amphetamine 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 amphetamine 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 for amphetamine involves deamination by cytochrome P450 to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidized to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation. Hydroxylation produces an active metabolite, O-hydroxynorephedrine, which acts as a false neurotransmitter and may account for some drug effect, especially in chronic users. Elimination and excretion: Normally 5 to 30% of a therapeutic dose of amphetamine 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: Amphetamine appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especialy norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Teratogenicity: The use of amphetamine for medical indications does not pose a significant risk to the fetus for congenital anomalies. Amphetamines generally do not appear to be human teratogens. 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 of amphetamine 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 of amphetamines. Sixty-five were followed children whose mothers were addicted to amphetamine during pregnancy, at least during the first trimester. 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 of amphetamine. Alcohol: may increase serum concentration of amphetamine. Ascorbic acid: lowering urinary pH, may enhance amphetamine excretion. Furazolidone: amphetamines may induce a hypertensive response in patients taking furazolidone. Guanethidine: amphetamine inhibits the antihypertensive response to guanethidine. Haloperidol: limited evidence indicates that haloperidol may inhibit the effects of amphetamine but the clinical importance of this interaction is not established. Lithium carbonate: isolated case reports indicate that lithium may inhibit the effects of amphetamine. Monoamine oxidase inhibitor: severe hypertensive reactions have followed the administration of amphetamines to patients taking monoamine oxidase inhibitors. Norepinephrine: amphetamine abuse may enhance the pressor response to noradrenaline. Phenothiazines: amphetamine may inhibit the antipsychotic effect of phenothiazines, and phenothiazines may inhibit the anorectic effect of amphetamines. Sodium bicarbonate: large doses of sodium bicarbonate inhibit the elimination of amphetamine, thus increasing the amphetamine effect. Tricyclic antidepressants: theoretically increases the effect of amphetamine, but clinical evidence is lacking. /Chlorphentermine hydrochloride/

The effect of chlorphentermine, in the form of chlorphentermine hydrochloride, induced alveolar changes on nitrogen dioxide toxicity was studied in mice. Male Swiss Webster mice were given 0 or 120 mg/kg chlorphentermine hydrochloride daily for 14 days followed by 48 hr exposure to 20 ppm nitogen dioxide. The animals were observed for clinical signs of toxicity. Selected mice were killed immediately or 1, 3, 5, and 7 days after nitogen dioxide exposure, the lungs were removed, sectioned, and examined by light and electron microscopy. In a second study using the same protocol, the total numbers of type I, type II, and alveolar macrophages were counted in lung sections. Chlorphentermine hydrochloride alone induced a diffuse accumulation of large foaming macrophages within alveoli. The cytoplasm of the macrophages contained vacuoles some of which had lamellar inclusions. Nitogen dioxide alone caused 20.8% mortality in the histopathology study and 18.5% mortality in the cell count study. No deaths occurred in any groups receiving chlorphentermine hydrochloride. nitogen dioxide caused type II cell hyperplasia and pulmonary edema, most notably in mice killed during the first 24 hr. These effects were less pronounced in mice pretreated wit phentermine. In the cell count study, nitogen dioxide alone significantly increased the number of type I and type II cells. These increases were not as large in animals given chlorphentermine hydrochloride. All treatments increased the number of macrophages. The largest increase occurred in mice given chlorphentermine hydrochloride plus nitogen dioxide on day 0; this leve changed only slightly through day five. The number of macrophages induced by nitogen dioxide alone increased steadily through day three. Changes induced by chlorphentermine hydrochloride partially protect against nitogen dioxide toxicity.|We have previously demonstrated that the chlorphentermine induced impairment in lymphocyte blastogenesis involves drug-induced inhibition of an event which occurs very early during lymphocyte activation. An early event, which is associated with mitogen induced lymphocyte activation, involves the hydrolysis of phosphatidylinositol by phospholipase C to yield inositol phosphates and diacylglycerol as products. Inositol phosphates and diacylglycerol then function as mediators of a trans-membrane signal for the continuation of the cellular response. It was the purpose of the present study to determine the effects of chlorphentermine on this phosphatidylinositol pathway. We demonstrated that formation of inositol phosphates in lymphocytes increases progressively above control over a 2 hr period following concanavalin A (Con A)-stimulation. In contrast, lymphocytes pre-incubated with 10(-5)M chlorphentermine for 60 min, then stimulated with Con A for 2 hr in the presence of 10(-5)M chlorphentermine, exhibit a significantly depressed inositol phosphate formation. In addition, chlorphentermine also inhibited the activity of phospholipase C (IC50 = 0.58 mM), the enzyme responsible for the formation of inositol phosphates during lymphocyte activation. Further, lymphocytes activated in a manner that bypasses the phosphatidylinositol pathway are not inhibited by 10(-7)M or 10(-9)M chlorphentermine as are cells activated with Con A. These results suggest that the suppression of the phosphatidylinositol pathway may be involved in the inhibition by chlorphentermine of lymphocyte blastogenesis induced by Con A.|A study was done in mice to assess any morphological, biochemical, or functional changes in alveolar macrophages following induction of lipidosis by chlorphentermine and/or inhalation of nitrogen dioxide. Male Swiss Webster mice were treated with 120 mg/kg chlorphentermine or water by gavage daily for 14 days. Following this, mice were exposed to air or 20 ppm nitrogen dioxide for 48 hr. Alveolar macrophages were obtained by bronchoalveolar lavage and tested for viability and function. Significantly greater numbers of total white cells and macrophages were obtained from mice treated with chlorphentermine and/or nitrogen dioxide. The percentage of macrophages was significantly lower in mice receiving the combination treatment. Neither treatment altered macrophage viability. The percentage of positive cells in the metabolic reduction assay was not altered by any treatment, while the total number positive was significantly increased by combined treatment. Decreased 5'-nucleotidase activity was found with chlorphentermine and/or nitrogen dioxide, and phagocytic capacity and activity were increased in these groups. Combination treatment gave the greatest total phagocytic capacity. Yeast killing was decreased by chlorphentermine and/or nitrogen dioxide, particularly with combined treatment. Increases found in total reduction and total yeast killing were related to increased macrophage numbers. The authors conclude that large increases in alveolar macrophages in lipidotic lung airways may protect the alveolar epithelium by quenching free radicals produced during nitrogen-dioxide induced lipid peroxidation.

LD50 MICE ORAL 270 MG/KG /CHLORPHENTERMINE HYDROCHLORIDE/|LD50 MICE SUBCUTANEOUS 267 MG/KG /CHLORPHENTERMINE HYDROCHLORIDE/

Used as an appetite suppressant.

Sympathomimetics|ANOREXIGENIC SYMPATHOMIMETIC WITH VERY LITTLE CENTRAL STIMULANT ACTIVITY. ITS CARDIOVASCULAR EFFECTS ARE ALSO WEAK, SO THAT DRUG HAS BEEN RECOMMENDED ESP FOR USE IN TREATMENT OF OBESITY COMPLICATED BY CARDIOVASCULAR DISORDERS. /CHLORPHENTERMINE HYDROCHLORIDE/|IT SHOULD BE PRESCRIBED ONLY AS SHORT-TERM ADJUNCT (4-6 WK) IN PROGRAM THAT ALSO INCLUDES CALORIC RESTRICTION, APPROPRIATE EXERCISE, & PSYCHOLOGIC SUPPORT. /CHLORPHENTERMINE HYDROCHLORIDE/|ANOREXIC /FORMER USE/

DESPITE ABSENCE OF REPORTS OF ABUSE, IT IS POSSIBLE THAT LONG-TERM USE, ESP OF LARGER THAN USUAL THERAPEUTIC DOSES, MAY RESULT IN PSYCHIC & PHYSICAL DEPENDENCE. /CHLORPHENTERMINE HYDROCHLORIDE/|CHLORPHENTERMINE IS CONTRAINDICATED IN GLAUCOMA & IN PATIENTS UNDER TREATMENT WITH MONOAMINE OXIDASE INHIBITORS. /CHLORPHENTERMINE HYDROCHLORIDE/|GENERALLY, ANOREXIANTS SHOULD NOT BE PRESCRIBED FOR PATIENTS WITH ... HYPERTHYROIDISM BECAUSE THEIR SYMPATHOMIMETIC EFFECT MAY AGGRAVATE THESE CONDITIONS. ... USED WITH CAUTION IN PATIENTS ... SENSITIVE TO ADRENERGIC AGENTS & ... NOT ... GIVEN TO THOSE KNOWN TO BE SUSCEPTIBLE TO DRUG ABUSE. /ANOREXIANTS/|CENTRAL STIMULANT & ANORECTIC EFFECTS OF MOST OF THESE DRUGS HAVE PROVEN INSEPARABLE. THIS PREVENTS THEIR USE IN LATTER PART OF DAY; GIVEN AFTER 4 PM, THEY INTERFERE WITH SLEEP @ NIGHT. /ANOREXIANTS/|For more Drug Warnings (Complete) data for CHLORPHENTERMINE (6 total), please visit the HSDB record page.

TOLERANCE TO EFFECT OF THESE AGENTS MAY OCCUR WITHIN SEVERAL WK. IF THIS IS OBSERVED, ANOREXIANTS SHOULD BE DISCONTINUED. /ANOREXIANTS/

Chlorphentermine is a relatively weak stimulant with little abuse potential. It presents a prominent serotonergic profile leading to pulmonary hypertension and cardiac fibrosis after prolonged use. Thus, this drug is no longer used.

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. (See all compounds classified as Sympathomimetics.)

Well absorbed following oral administration.|CHLORPHENTERMINE HAS GREATER TISSUE:BLOOD RATIO IN RATS THAN PHENTERMINE, & TISSUE ACCUMULATION OF CHLORO-DERIV INCR RELATIVE TO PLASMA LEVELS AFTER CHRONIC DOSING.|IN MICE, UNIDENTIFIED CONJUGATE (60% OF DOSE), WHICH IS NEITHER GLUCURONIDE NOR N-ACETYL DERIV, WAS NOT FORMED BY LIVER MICROSOMES, BUT IN RATS, CHLORPHENTERMINE IS EXCRETED UNCHANGED IN URINE.|FOLLOWING ORAL ADMIN TO MAN, N-OXIDATION TAKES PLACE & UNDER NORMAL CONDITIONS OF URINARY PH, URINE IS MAIN ELIMINATION ROUTE FOR CHLORPHENTERMINE; ACIDIFYING THE URINE INCR URINARY EXCRETION OF UNCHANGED DRUG @ EXPENSE OF N-OXIDIZED PRODUCTS.

... CHLORPHENTERMINE IS METABOLIZED VIA UNRECOGNIZED ROUTE TO AFFORD UNUSUAL CONJUGATE, WHICH IS NEITHER GLUCURONIDE NOR N-ACETYL DERIV, IN URINE OF MOUSE, WHEREAS IN RAT CHLORPHENTERMINE IS EXCRETED UNCHANGED.

40 hours

MOST ANOREXIANTS ARE STIMULANTS OF CNS ... RESULTS OF ... ANIMAL STUDIES HAVE SUGGESTED, BUT NOT PROVED, THAT ALL ANOREXIANTS EXCEPT MAZINDOL ... AFFECT APPETITE CONTROL CENTERS OF HYPOTHALAMUS ... . /ANOREXIANTS/|MOST ANOREXIANTS ARE STIMULANTS OF CNS ... .|The binding of chlorphentermine to phospholipids in alveolar lavage materials and lung cells was studied in rats. In a preliminary experiment, lungs removed from male Sprague Dawley rats were lavaged. The lavage fluid was incubated with 10 mM chlorphentermine and 50 micromolar 1-anilino-8-naphthalene sulfonate. After differential centrifugation, the extent of binding of chlorphentermine to phospholipids in the various lavage fractions was determined using a fluorometric assay based on 1-anilino-8-naphthalene sulfonate. Chlorphentermine was bound equally to phospholipids in all fractions. Male Sprague Dawley rats were injected with 25 mg/kg (14)C labeled chlorphentermine daily for 3 days. They were killed 24 hr after the last dose and the lungs were removed and lavaged. The extent of chlorphentermine/phospholipid binding in the cell free whole lavage fluid, alveolar macrophages, type II cells, and other pneumocytes was determined. Chlorphentermine was bound to phospholipids in whole lavage fluid in a 1:100 mole ratio. Chlorphentermine bound to phospholipids in the alveolar macrophages, type II cells, and other lung lung cells in mole ratios of 1:18, 1:33, and 1:333, respectively. The authors conclude that chlorphentermine binds to pulmonary surfactant phospholipids in vitro. In vivo, it binds to phospholpids in at least three different compartments: acellular lavage fluid, alveolar macrophages, and type II cells. The interaction of chlorphentermine with phosphoplipids may impair phospholipid degradation resulting in phospholipidosis in surfactant materials and alveolar macrophages.

Diazepam may be given to control central nervous system stimulation and convulsions. For marked excitement or hallucinations chlorpromazine may be necessary and, in addition, its alpha-adrenoceptor blocking properties may be useful for the management of hypertension. Severe hypertension may call for the administration of an alpha-adrenoceptor blocking agent, such as phentolamine. Measures should be taken to control increased body temperature.

DYSPEPSIA HAS BEEN ASSOCIATED WITH ITS ADMIN. /CHLORPHENTERMINE HYDROCHLORIDE/|INSOMNIA, NERVOUSNESS, DIZZINESS, & PALPITATION OCCASIONALLY OCCUR. /CHLORPHENTERMINE HYDROCHLORIDE/|IT IS SAID TO PRODUCE MYDRIASIS WHEN GIVEN SYSTEMICALLY ...|Chlorophentermine hydrochloride ... is used as an appetite depressant, but it does not alter the flicker fusion frequency in normal patients in the manner of drugs having considerable central stimulatory effect. It is said to produce slight mydriasis when given systemically and on this basis there has been apprehension about its use in glaucoma, but there have been no reports of precipitation or aggravation of angle-closure glaucoma, and it seems extremely unlikely that the drug would have adverse action in chronic open-angle glaucoma. ... /Chlorphentermine hydrochloride/

Avipron

Chlorphentermine|Pre-Sate, Lucofen, Apsedon, Desopimon|1645|Schedule III - Substances in the DEA Schedule III have a potential for abuse less than substances in Schedules I or II and abuse may lead to moderate or low physical dependence or high psychological dependence.|No

... CHLORPHENTERMINE HYDROCHLORIDE (PRE-SATE), 65-MG SLOW-RELEASE TABLETS ... . /HYDROCHLORIDE/

... CHLORPHENTERMINE [PRE-SATE] ... /IS/ CLASSIFIED AS SCHEDULE III ... /DRUG/. /CHLORPHENTERMINE HYDROCHLORIDE/

A procedure for screening for amphetamine type drugs by thin layer chromatography is developed. ... This technique has been evaluated by the mean list method. The procedure involves combined use of normal and reversed phase thin layer chromatography and visualization with Fast Black K salt. All the amphetamine cmpd tested were equally reactive with Fast Black K salt, the detection limit being 0.1 ug, and could be readily classified, according to the color of the spots, into primary and secondary amines. The combined use of the chromatography systems and the color reaction generaklly enabled differentiation of amphetamine derivatives from other drugs and in most cases from each other.

GAS LIQUID CHROMATOGRAPHIC METHOD FOR DETERMINING CHLORPHENTERMINE IN URINE IS PRESENTED. METHODS ARE ALSO REPORTED TO DETERMINE CONJUGATED & TOTAL METABOLITES OF CHLORPHENTERMINE.|Capillary column gas liquid chromatography was used for the analysis of urine samples for drugs of abuse. Extraction into butyl acetate is followed by temperature programmed analysis from 90 to 310 deg to provide a comprehensive screen for basic drugs. Retention data are presented for 266 cmpd. ...

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