Avtor/Urednik		Šprah, Lilijana
Naslov		Dopaminergična aktivnost ergolinskega derivata LEK-8829
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Medicinska fakulteta
Leto izdaje		1997
Obseg		str. 94
Jezik		slo
Abstrakt		1.) Previous experiments have suggested a potential atypical antipsychotic activity of the ergoline derivative LEK-8829. In vitro experiments showed a high affinity to 5-HT1A, 5-HT2 and D-2 receptors and a moderate affinity to D-1 receptors. The ratio of pKi values 5-HT2/D-2=1, 11 was similar to the ratio of atypical antipsychotic clozapine (1.13). In vivo experiments showed an antagonism of dopamine and 5-hydroxytryptamine (5-HT) receptor linked behaviours. 2.) In the present study, the rats with unilateral lesions of dopamine nigrostriatal neurons with 6-hydroxydopamine (6-OHDA model), were used to determine the activity of LEK-8829 on dopamine receptor D-1 and D-2. 3.) The administration of LEK-8829 induced a long lasting contralateral turing behaviour that was dose dependent. The turing was mediated via D-1 receptors, since the antagonist SCH-23390 but not the D-2 receptor antagonist halopelidor or 5-HT1A antagonist pindolol, dose-dependently inhibited the turning behaviour induced by LEK-8829. 4.) Similar contralateral turing profiles induced by LEK-8229 (0.25 mg/kg) or SKF-89258 (0.25 mg/kg) also points to D-1 agonism of LEK-8829. Both profiles of contralateral turing showed a "peak" in the first ten minutes after injection and the intensity ofcontralateral turing was also similar. The high dose of haloperidol inhibited the intensity turning and prolonged the duration of turning behaviour induced either by LEK-8829 or by SKF-89258. Pindolol increased the total number of turns due the prolongation of turning behaviour induced by LEK-8829 or SKF-89258. 5.) Bromocriptine induced intensive, long lasting turning behaviour with long latency that was inhibited by haloperidol but not with SCH-23390. 6.) The D-2 receptor mediated inhibition of turning behaviour by LEK-8829 was also shown. Namely, the contralateral turing induced by bromocriptine was inhibited by coadministration of SCH-23390 and LEK-8829. (Abstract truncated at 2000 characters.)
Deskriptorji		CORPUS STRIATUM ERGOLINES BEHAVIOR, ANIMAL MOVEMENT DISORDERS DOPAMINE AGONISTS RATS, WISTAR RECEPTORS, DOPAMINE D1 RECEPTORS, DOPAMINE D2 APOMORPHINE HALOPERIDOL PINDOLOL BROMOCRIPTINE OXIDOPAMINE