Interaction of beta-carbolines with central dopaminergic transmission in mice: structure-activity relationships.
G Pimpinella, M Palmery
Neuroscience Letters April 14, 1995 DOI: 10.1016/0304-3940(95)11469-d (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Harmaline Harmine 6-methoxy-harmalan 6-methoxy-harman Harman 6-Methoxy-tetrahydro-beta-carbolin (6-MeO-THBC) Tetrahydro-beta-carbolin (THBC) Nimodipine L-DOPA |
| Dose | Harmaline 0.075, 0.15 and 0.35 mg/kg; harmine 0.15, 0.35 and 0.75 mg/kg; 6-methoxy-harmalan, 6-methoxy-harman and harman 3 mg/kg; 6-MeO-THBC 3 mg/kg; THBC up to 3 mg/kg; nimodipine 2.5 mg/kg; L-DOPA 250 mg/kg |
| Key findings | Harmaline and harmine strongly enhanced L-DOPA (250 mg/kg)-induced stereotypy in mice at low doses, while 6-methoxy-harmalan, 6-methoxy-harman and harman were far less potent, acting only at 3 mg/kg; 6-MeO-THBC had only a weak effect at 3 mg/kg and THBC had none. Nimodipine (2.5 mg/kg) only slightly antagonized harmaline's facilitation. |
Abstract
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.
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