Antiparkinsonian potential of interaction of LEK-8829 with bromocriptine
| Autor: | Marko Živin, Lilijana S̆prah, Dusan Sket |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Agonist
Male medicine.medical_specialty Psychosis medicine.drug_class Pharmacology Motor Activity Antiparkinson Agents Dopamine receptor D1 Dopamine Dopamine receptor D2 Internal medicine medicine Animals Rats Wistar Bromocriptine Lysergic Acid business.industry Benzazepines medicine.disease Rats Endocrinology Dopamine receptor Dopamine Antagonists Haloperidol Serotonin Stereotyped Behavior business medicine.drug |
| Zdroj: | European journal of pharmacology. 349(2-3) |
| ISSN: | 0014-2999 |
| Popis: | The ergoline derivative, LEK-8829 (9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline), has been proposed as a potential atypical antipsychotic drug with antagonistic actions at dopamine D2 and serotonin 5-HT2 and 5-HT1A receptors ( Krisch et al., 1994 , Krisch et al., 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-methyl-1-phenyl-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-α-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 cumulated 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 LEK-8829/bromocriptine treatment. We conclude that in the 6-hydroxydopamine model, the turning behaviour mediated by the LEK-8829/bromocriptine 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. Therefore, LEK-8829 may have a potential for the therapy of parkinsonism complicated by dopamine D2 receptor agonist drug-induced psychosis. |
| Databáze: | OpenAIRE |
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