Possible Interaction: Cocaine and Mazindol

“Furthermore, mazindol treatment may increase the cardiovascular risks of cocaine.”

“ Mazindol is a catecholamine reuptake inhibitor that blocks binding of cocaine at the dopamine reuptake site.”

“There were significant interactions between the effects of cocaine and mazindol on heart rate and blood pressure, with combinations producing significantly large and more sustained increases compared with cocaine alone.”

“This transport is blocked … psychostimulant drugs cocaine , l- and d-amphetamine, and phenyclidine), neurotoxins (6-hydroxydopamine and N-methyl-4-phenylpyridine (MPP))+), neurotransmitters (epinephrine, …, gamma-aminobutyric acid, and serotonin), antidepressants (amitriptyline, bupropion, desipramine, mazindol, nomifensine, and nortriptyline), and various uptake inhibitors ( mazindol , GBR 12783, GBR 12909, and amfonelic acid).”

“The present results suggest that complex interactions reported between cocaine and mazindol in inhibiting dopamine transport are beyond the level of ligand recognition.”

“Some of these drugs (100 μmol/l dopamine, 1 μmol/l mazindol or 100 μmol/l cocaine) protected the specific binding of [3H]cocaine against the effects of pHMBS, whereas 1 mmol/1 p-tyramine, 10 μmol/l nomifensine and 10 nmol/l GBR 12783 were ineffective.”

“Previous exposure to cocaine significantly affected locomotor activity and stereotopy-like behavior produced by cocaine, mazindol , RTI-55, and GBR12909.”

“The specific binding of [3H]cocaine was inhibited monophasically by GBR 12783, mazindol , nomifensine and substrates of the transporter; in saturation experiments, GBR 12783 competitively blocked the [3H]cocaine specific binding and vice versa.”

“In contrast, mazindol and nomifensine were found to bind to separate interactive sites when individually paired with cocaine.”

“Six new N-sulfonylated analogs of cocaine have been prepared, and these compounds have been evaluated for their ability to inhibit [3H]mazindol binding and [3H]dopamine uptake into striatal synaptosomes.”

“injections of cocaine (0.1-1.7 mg/kg), D-amphetamine (….1-1 mg/kg) and the dopamine re-uptake inhibitor mazindol (0.03-0.56 mg/kg) given 5 … before the session decreased self-administration of cocaine , but also decreased rates of behavior … by the presentation of food.”

“The self-administration of cocaine was compared with that of bupropion, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, mazindol , methylphenidate and nomifensine, drugs that displace [3H]cocaine from its binding sites and have monoamine uptake inhibiting effects in common with those of cocaine.”