Mazindol

Toxicity

Symptoms of mazindol overdose may be associated with restlessness, tremor, rapid breathing, confusion, hallucinations, panic, aggressiveness, nausea, vomiting, diarrhea, an irregular heartbeat, and seizures.

Chemical properties

White Solid

Originator

Sanorex ,Sandoz ,US ,1973

The Uses of Mazindol

Clinical trials as appetite depressant. Anorexic; CNS stimulant. Controlled substance (stimulant).

Indications

Used in short-term (a few weeks) treatment of exogenous obesity in conjunction with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of 30 kg of body weight per height in meters squared (kg/m2) or in patients with a body mass index of 27 kg/m2 in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia.

Background

Mazindol is a tricyclic anorexigenic agent that is unrelated to and less toxic than amphetamine, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter. Mazindol is only approved in the United States for the treatment of Duchenne muscular dystrophy, and is not marketed or available in the United States for use in the treatment of obesity.

Definition

ChEBI: Mazindol is an organic molecular entity.

Manufacturing Process

Step 1: 1-(p-Chlorophenyl)-3-Ethoxy-11H-Isoindole - Crystalline triethyloxonium borontetrafluoride (21 g) (prepared from 23 g of borontrifluoride etherate and 11 g of epichlorohydrin) is dissolved in 100 ml of absolute methylenechloride. 3-(p-Chlorophenyl) phthalimidine (21 g) is added and the reaction mixture is stirred overnight at room temperature. The resulting solution is poured onto 50 ml of saturated sodium carbonate, extracted with 500 ml of ether and dried. Upon evaporation of the solvent there is obtained crude material which is recrystallized from methylene chloride/hexane (1:1) to yield 1-(p-chlorophenyl)-3-ethoxy-1H-isoindole; MP 102° to 103°C.
Step 2: 5-(p-Chlorophenyl)-5-Hydroxy-2,3-Dihydro-5H-Imidazo[2,1- a]Isoindole - 1-(p-Chlorophenyl)-3-ethoxy-1H-isoindole (1 g), 2 g of ethyleneimine hydrotetrafluoroborate moistened with methylene chloride (containing approximately 0.66 g of dry salt) is refluxed in 25 ml of absolute toluene for 2 hours in an atmosphere of nitrogen. The resulting mixture is poured into 2 N sodium carbonate solution (25 ml) and extracted with ether. The ether solution is contacted with air for 6 days at room temperature to give the desired product. The crude material is recrystallized from acetone/hexane (1:1) to give 5-(p-chlorophenyl)-5-hydroxy-2,3-dihydro-5Himidazo[2,1-a]isoindole; MP 198° to 199°C.

brand name

Mazanor (Wyeth); Sanorex (Novartis);Dasten;Degonon;Fagolipo;Lipese;Magrilan;Mazanor tablets;Mazeldene;Mazinil;Maznor;Tenorac.

Therapeutic Function

Antiobesity

World Health Organization (WHO)

Mazindol, an anorectic agent, was introduced into medicine in 1970 as an aid to weight reduction. It is controlled under Schedule IV of the 1971 Convention on Psychotropic Substances. It remains available in many countries with highly evolved drug regulatory authorities. (Reference: (UNCPS4) United Nations Convention on Psychotropic Substances (IV), , , 1971)

Pharmacokinetics

Mazindol is a sympathomimetic amine that stimulates the central nervous system (nerves and brain), leading to increased your heart rate and blood pressure, and decreased appetite. Since the appetite-suppressing effect of the drug tends to decrease after few weeks of treatment, sympathomimetic appetite suppressants are typically used short-term weight-loss program.

Metabolism

Hepatic.