Interaction of beta-carbolines with central dopaminergic transmission in mice: structure-activity relationships.
Although several beta-carboline alkaloids display hallucinogenic properties in humans, their mechanism of action remains unclear. To ascertain their influence on central dopaminergic transmission, in this study we investigated the facilitating effect of low doses of various beta-carbolines on L-DOPA (250 mg/kg)-induced stereotypy in mice. Harmaline (0.075, 0.15 and 0.35 mg/kg) and harmine (0.15, 0.35 and 0.75 mg/kg) powerfully enhanced the degree of stereotypy, whereas 6-methoxy-harmalan, 6-methoxy-harman and harman were far less potent, augmenting stereotypy only at much higher doses (3 mg/kg). 6-Methoxy-tetrahydro-beta-carbolin (6-MeO-THBC) had only a weak effect at the dose of 3 mg/kg and tetrahydro-beta-carbolin (THBC) had no effect up to the dose of 3 mg/kg. The Ca(2+)-channel blocker nimodipine (2.5 mg/kg) only slightly antagonized harmaline (0.15 mg/kg) facilitation of L-DOPA-induced stereotypy.
Pimpinella
G
G
Institute of Pharmacology and Pharmacognosy, University of Rome La Sapienza, Italy.
Palmery
M
M
D000818:Animals; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D009553:Nimodipine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects*
D002243:Carbolines; D007980:Levodopa; D009553:Nimodipine; D004298:Dopamine