Mazindol is a stimulant

Stimulant

Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

 drug

Drug

A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 of the tetracyclic

Tetracyclic

Tetracyclic may refer to* any of a number of cyclic compounds containing four rings. They have various pharmaceutical uses; see Tetracyclic drug group.* cyclic flowers constructed of four whorls....

 chemical class which is used as an anorectic

Anorectic

An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...

. It was developed by Sandoz-Wander in the 1960s

Indications

Mazindol is used in short-term (i.e., a few weeks) treatment of exogenous obesity

Obesity

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

, in combination with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification

Behavior modification

Behavior modification is the use of empirically demonstrated behavior change techniques to increase or decrease the frequency of behaviors, such as altering an individual's behaviors and reactions to stimuli through positive and negative reinforcement of adaptive behavior and/or the reduction of...

 in patients with a body mass index

Body mass index

The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...

 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

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, diabetes, or hyperlipidemia

Hyperlipidemia

Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...

.

Pharmacology

Mazindol is a sympathomimetic amine

Sympathomimetic amine

Sympathomimetic drugs mimic the effects of transmitter substances of the sympathetic nervous system such as catecholamines, epinephrine , norepinephrine , dopamine, etc...

, which is similar to amphetamine

Amphetamine

Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

. It stimulates the central nervous system

Central nervous system

The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

, which increases heart rate and blood pressure

Blood pressure

Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

, and decreases appetite

Appetite

The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

. Sympathomimetic anoretics (appetite suppressants) are used in the short-term treatment of obesity. Their appetite-reducing effect tends to decrease after a few weeks of treatment. Because of this, these medicines are useful only during the first few weeks of a weight-loss program.

Although the mechanism of action of the sympathomimetics in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Like other sympathomimetic appetite suppressants, mazindol is thought to act as a reuptake inhibitor

Norepinephrine reuptake inhibitor

A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...

 of norepinephrine

Norepinephrine

Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

. In addition, it inhibits dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 and serotonin

Serotonin

Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 reuptake

Reuptake

Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....

. The recommended dosage is 2 mg per day for 90 days in patients with 40 kg of overweight or less, 4 mg a day in patients with more of 50 kg of overweight, separated in two ingestion with a 12 hour window between each 2 mg dose.

Overdose

Symptoms of a mazindol overdose include: restlessness

Psychomotor agitation

Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

, tremor

Tremor

A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...

, rapid breathing, confusion

ConFusion

ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...

, hallucination

Hallucination

A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, panic

Panic

Panic is a sudden sensation of fear which is so strong as to dominate or prevent reason and logical thinking, replacing it with overwhelming feelings of anxiety and frantic agitation consistent with an animalistic fight-or-flight reaction...

, aggressiveness, nausea

Nausea

Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, vomiting

Vomiting

Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, diarrhea

Diarrhea

Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, an irregular heartbeat, and seizure

Seizure

An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s.

Synthesis

(Satendra Singh, 2000) pages 87-90

Analogs

From considering the attached QSAR table we can make the apparent observations:

1. Desoxylation of the tertiary alcohol in mazindol improves DAT and SERT binding. The compound now behaves as a functional SNDRI instead of predominantly a noradrenaline reuptake inhibitor.
2. Removal of the p-chloro atom in mazindol means that the compound now only behaves as a noradrenaline reuptake inhibitor.
3. Changing the size of the imidazoline
   Imidazoline
   Imidazoline is a nitrogen-containing heterocycle with formula C3H6N2, derived from imidazole. The ring contains an imine bond, and the carbons at the 4 and 5 positions are singly bonded, rather than doubly bonded for the case of imidazole...
   
    type ring system in mazindol to the corresponding six-membered homolog increases potency of the resultant compound at the DAT by approximately ten-fold.

n	R	R'	R"	hSERT	hNET	hDAT
1	Cl	H	OH	94	4.9	43
1	Cl	H	H	15	6.9	6.0
1	H	H	OH	2140	2.8	730
1	-C4H4-		OH	1.8	4.5	66
2	Cl	H	OH	53	4.9	3.7
2	OH	H	OH	60	1.9	59.0
2	OMe	H	OH	94	4.1	30.4
2	-OCH2O-		OH	83	0.62	2.21

To make the six membered (so-called homomazindol) analog, one can simply substitute 1,2-diaminoethane with 1,3-diaminopropane. Importantly, another procedure was also published.

Given the data in the above table, one might also be interested in making the desoxy-mazindol analog. The synthesis for this is facile. Although "mazindane" is relatively stable in air, it is readily oxidized to mazindol upon contact with monoamine oxidaze enzymes present at the DAT.

See also: SNDRI for context.