Dopamine autoreceptor agonists as potential antipsychotics. 1. (Aminoalkoxy)anilines.
The synthesis and pharmacological properties of a novel type of [(arylpiperazinyl)alkoxy]anilines with dopaminergic properties are described. One of these compounds, 3-[3-(4-phenyl-1-piperazinyl)propoxy]benzenamine (4c), has been identified as a selective dopamine (DA) autoreceptor agonist in tests that include [3H]haloperidol binding, inhibition of striatal DA synthesis, inhibition of DA neuronal firing, inhibition of spontaneous locomotor activity, and reversal of reserpine-induced depression in rats. In addition, 4c possesses good oral activity in the Sidman conditioned avoidance test in squirrel monkeys, which is indicative of antipsychotic activity. In a primate model, 4c was found to lack the liability for extrapyramidal side effects usually associated with antipsychotic drugs.
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D012453:Saimiri; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D014150:Antipsychotic Agents; D011954:Receptors, Dopamine