Antidepressant profile of 9-methyl-2[-3-(4-phenyl-1-piperazinylpropyl)]-1,2,3,4-tetrahydro-beta- carbolin-1-one (B-193).
A potential antidepressant activity of B-193 was studied in mice and rats. In in vitro studies B-193 did not affect the uptake of NA and 5-HT. In in vivo models the tested compound did not influence the reserpine-induced hypothermia, hypoactivity and ptosis, the stimulating action of L-DOPA, the apomorphine-induced hypothermia. On the other hand, it produced a positive effect in the despair test. When given repeatedly, it evoked adaptive changes in brain neurotransmitter receptors, i.e. it decreased the density of beta-adrenoceptors and increased the number of alpha 1 ones; those changes were accompanied with functional alternations in the reactivity of those receptors: an attenuated behavioral reaction to salbutamol and enhanced aggressiveness induced by a high dose of clonidine. Furthermore, B-193 administered repeatedly enhanced hyperlocomotion induced by amphetamine but did not influence the stereotypy induced by apomorphine. These results indicate that B-193 possesses properties characteristic for atypical antidepressants.
Wiczyńska
B
B
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Antkiewicz-Michaluk
L
L
Pilc
A
A
Chojnacka-Wójcik
E
E
Przegaliński
E
E
D000374:Aggression / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001763:Blepharoptosis / Q000139:chemically induced; D001831:Body Temperature / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D000928:Antidepressive Agents; D002243:Carbolines; D010879:Piperazines; C062048:B 193; D012701:Serotonin; D007980:Levodopa; D012110:Reserpine; D008995:Monoamine Oxidase; D003000:Clonidine; D001058:Apomorphine; D009638:Norepinephrine