| Author/Editor | Živin, Marko; Šprah, Lilijana; Sket, Dušan | |
| Title | Antiparkinsonian potential of interaction of LEK-8829 with bromocriptine | |
| Type | članek | |
| Source | Eur J Pharmacol | |
| Vol. and No. | Letnik 349 | |
| Publication year | 1998 | |
| Volume | str. 151-7 | |
| Language | eng | |
| Abstract | The ergoline derivative, LEK-8829 (9,10-didehydro-N-methyl-(2-propyny)-6-methyl-8-aminomethylergoline), has been proposed as a potential atypical antipsychotic drug with antagonistic actions t dopamine D2 and serotonin 5-HT2 and 5-HT1A receptors (krisch et al., 1994, 1996). LEK-8829 also induces contralateral turning in rats with 6-hydroxydopamine-induced unilateral lesion of dopamine nigrostriatal neurons. Turning is blocked by SCH-23390 (R(+)-chloro-8-hydroxy-3-methy1-2,3,4,5-tetrahydro-1H-3-benzazepine), a dopamine D1 receptor antagonist. It has been suggested that LEK-8829 could have beneficial effects in parkinsonian patients suffering from psychotic episodes induced as a side-effect of antiparkinsonian treatment with dopamine D2 receptor agonists. Therefore, we now investigated the interaction of LEK-8829 with the dopamine D2 receptor agonist bromocriptine (2-bromo-alpha-ergokryptine) in 6-hydroxydopamine-lesioned rats. Treatment with either LEK-8829 (3 mg kg -1) or bromocriptine (3 mg kg -1) induced a vigorous contralateral turning response. The cumulated number of turns induced by the treatment with both drugs combined was not significantly different from the cummulated number of turns induced by single-drug treatment. The pretreatment with SCH-23390 (1 mg kg -1) did not have a significant effect on the bromocriptine-induced turning but significantly decreased the turning observed after the combined LRK-8829/bromocriptine treatment. We conclude that in the 6-hydroxydopamine model, the turning behaviour mediated by the LEK-8829/bromocritine combination may be the result of opposing activity of both drugs at dopamine D2 receptors with concomitant stimulation of dopamine D1 receptors by LEK-8829.(Abstract truncated at 2000 characters.) | |
| Descriptors | ANTIPARKINSON AGENTS DOPAMINE ANTAGONISTS LYSERGIC ACID STEREOTYPED BEHAVIOR RATS, WISTAR BROMOCRIPTINE HALOPERIDOL SCH-23390 MOTOR ACTIVITY |