Pharmacological evaluation of selected arylpiperazines with atypical antipsychotic potential.
Six active compounds, among previously synthesized and screened arylpiperazines, were selected and evaluated for the binding affinity to rat dopamine, serotonin and alpha(1) receptors. Two compounds with benztriazole group had a 5-HT(2A)/D(2) binding ratio characteristic for atypical neuroleptics (>1, pK(i) values). Compound 2, 5-[2-[4-(2,3-dimethyl-phenyl)-piperazin-1-yl]ethyl]1H-benzotriazole, expressed clozapine-like in vitro binding profile at D(2), 5-HT(2A) and alpha 1 receptors and a higher affinity for 5-HT(1A) receptors than clozapine. Also, it exhibited the noncataleptic behavioural pattern of atypical antipsychotics and antagonized d-amphetamine-induced hyperlocomotion in rats.
Tomić
Mirko
M
Department of Biochemistry, Institute for Biological Research, 29 novembra 142, 11060 Belgrade, Serbia and Montenegro. mitomic@ibiss.bg.ac.yu
Kundaković
Marija
M
Butorović
Biljana
B
Janać
Branka
B
Andrić
Deana
D
Roglić
Goran
G
Ignjatović
Djurdjica
D
Kostić-Rajacić
Sladjana
S
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects
D014150:Antipsychotic Agents; D010879:Piperazines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin