title: Effects of tandamine and pirandamine, new potential antidepressants, on the brain uptake of norepinephrine and 5-hydroxytryptamine and related activities.
abstract: Two novel agents, tandamine (TA; a thiopyrano (3,4-b) indole) and pirandamine (PA; an indeno (2,1-c)pyran), and the tricyclic antidepressants desimipramine (DMI), imipramine (I) and amitriptyline (A) were compared in various in vivo pharmacological tests and for norepinephrine (NE) and 5-hydroxytryptamine (5-HT) neuronal uptake inhibition. TA was found to be equivalent, or greater, in activity to DMI in blocking brain NE uptake, antagonizing reserpine-induced effects and potentiating the behavioural effects of l-Dopa. Similarly to DMI, TA did not appreciably block brain 5-HT uptake; unlike DMI, TA did potentiate central 5-HT activity at high doses. PA exerted an opposite profile to TA, being equivalent to A and greater than I as a 5-HT uptake blocker and central 5-HT potentiator; PA was not effective as a NE uptake blocker or potentiator. Neither TA or PA exhibited in vivo MAO inhibition, and in contrast to DMI, I and A, exhibited no central anticholinergic effects. TA, but not PA, potentiated apomorphine-induced gnawing. These findings indicate that TA is a relatively specific blocker of neuronal NE uptake and PA is a selective 5-HT uptake blocker.
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D007192:Indenes / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D051381:Rats; D012018:Reflex / Q000187:drug effects; D012110:Reserpine / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000378:metabolism*; D014439:Tyramine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D007192:Indenes; D007211:Indoles; D012701:Serotonin; D007980:Levodopa; D010095:Oxotremorine; D012110:Reserpine; D006916:5-Hydroxytryptophan; D001058:Apomorphine; D009638:Norepinephrine; D014439:Tyramine