Antipsychotic-like profile of alstonine.
Although recently developed drugs have brought significant improvement, the treatment of psychotic disorders still presents serious drawbacks. Because inherent complexity and lack of satisfactory understanding of the underlying pathophysiology impose limits for rational drug design, resourceful approaches in the search for antipsychotics are pertinent. This article reports pharmacological properties of alstonine, a heteroyohimbine-type alkaloid, which exhibited an antipsychotic-like profile, inhibiting amphetamine-induced lethality, apomorphine-induced stereotypy, and potentiating barbiturate-induced sleeping time. Atypical features of alstonine were the prevention of haloperidol-induced catalepsy and lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked to antipsychotic mechanism of action.
Costa-Campos
L
L
Depto. de Farmacologia, UFRGS, Porto Alegre, Brazil.
Lara
D R
DR
Nunes
D S
DS
Elisabetsky
E
E
D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D006220:Haloperidol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D046948:Secologanin Tryptamine Alkaloids / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D046948:Secologanin Tryptamine Alkaloids; C009244:serpentine (alkaloid); D000661:Amphetamine; D006220:Haloperidol; D001058:Apomorphine