Mazindol

Pharmacodynamics

Mazindol is a sympathomimetic amine, which is similar to amphetamine. It stimulates the central nervous system, which increases heart rate and blood pressure, and decreases appetite. 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 of norepinephrine, dopamine, and serotonin.

In addition to its other actions, mazindol has been found to act as a very-low-potency partial agonist of the orexin OX₂ receptor.^[14][3] It showed 35% binding inhibition at the human orexin OX₂ receptor at a concentration of 10,000 nM (a measure of binding affinity), an activational potency (EC₅₀Tooltip half-maximal effective concentration) of 16,000 nM, and an activational efficacy (E_maxTooltip maximal efficacy) of approximately 25 to 50%.^[14] This action is profoundly less potent than mazindol's monoamine reuptake inhibition.^[14] Whether the orexin OX₂ receptor partial agonism of mazindol occurs at clinically relevant concentrations or is pharmacologically significant is unclear.^[14]

Tautomers

Mazindol exhibits pH dependent tautomerization between the keto form and the cyclic hemiaminal. Mazindol exists in the tricyclic (-ol) form in neutral media and undergoes protonation to the benzophenone tautomer in acidic media. QSAR studies have indicated that the ability of mazindol to inhibit NE and DA reuptake may be mediated by the protonated (benzophenone) tautomer.^[15]

Synthesis

The chemical synthesis of mazindol has been described.^{[16][17][18][4][19]}

Related compounds

Some analogues and related compounds include ciclazindol, setazindol, trazium, dazadrol, and AW-15'1129, among others.

Attention deficit hyperactivity disorder

As of 2016 mazindol was being studied in clinical trials for attention-deficit hyperactivity disorder (ADHD).^[23] There is a Swiss study investigating its efficacy in treating attention deficit hyperactivity disorder (ADHD).^[24]