Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 D2 receptors (the ratio of pKi values 5-HT2/D2 = 1.11) and a moderate affinity to D1 receptors. In vivo experiments showed antagonism of dopamine and 5-hydroxytryptamine (5-HT) receptor-linked behaviours. 2. In the present study, the rats with unilateral dopaminergic deafferentation of the striatum, induced by the lesion of the median forebrain bundle with 6-hydroxydopamine (6-OHDA), were used to determine the effects of LEK-8829 on turning behaviour and on striatal c-fos mRNA levels. 3. The administration of LEK-8829 induced a long lasting contralateral turning behaviour that was dose-dependent. It was found that the specific D1 receptor antagonist SCH-23390 but not the D2 receptor antagonist haloperidol or 5-HT1A antagonist pindolol, dose-dependently inhibited the turning behaviour induced by LEK-8829. 4. In an attempt to clarify the D1:D2 receptor interactions involved in the action of LEK-8829 in the 6OHDA model, we used in situ hybridization histochemistry to compare the effect of SCH-23390 pretreatment on striatal c-fos mRNA expression induced either by LEK-8829 or by the typical antipsychotic haloperidol. 5. LEK-8829 induced a bilateral striatal c-fos mRNA expression that was significantly higher in the denervated striatum as compared to the intact striatum and was completely blocked on both sides by pretreatment with SCH-23390. In contrast, haloperidol-induced striatal c-fos mRNA expression was limited to the innervated striatum and was not blocked by SCH-23390. 6. Our data demonstrate an intrinsic activity of LEK-8829 on D1 receptors that is potentiated in the dopamine-depleted striatum. We conclude, therefore, that the putative atypical antipsychotic LEK-8829 may prove useful as an experimental tool for the study of D1:D2 receptor interactions and could have beneficial effects in the treatment of drug-induced psychosis in patients with Parkinson's disease.
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PMID:The D1 receptor-mediated effects of the ergoline derivative LEK-8829 in rats with unilateral 6-hydroxydopamine lesions. 893 22

The ergoline derivative, LEK-8829 (9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylerg oline), 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, 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-benzaze pine), 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 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.
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PMID:Antiparkinsonian potential of interaction of LEK-8829 with bromocriptine. 967 Oct 92

Psychostimulant-induced behavioral sensitization is an experimental model of the stimulant psychosis and the vulnerability to relapse in schizophrenia. This study investigated the effects of aripiprazole, an antipsychotic drug that has dopamine D2 receptor partial agonist activity, on established sensitization induced by methamphetamine (MAP) in mice. Repeated treatment with MAP (1.0mg/kg, s.c.) for 10 days progressively increased the ability of MAP to increase locomotor activity. The enhanced locomotion induced by a challenge dose of MAP (0.24 mg/kg, s.c.) also occurred after withdrawal from MAP pretreatment. Repeated treatment with aripiprazole from days 10 to 14 during withdrawal from MAP administration attenuated the effect of MAP pretreatment, enhancing the motor response to a challenge dose of stimulant 3 days after the aripiprazole preparation. In contrast, sulpiride, a dopamine D2 receptor specific antagonist, and risperidone, a serotonin 5-HT2 and dopamine D2 receptor antagonist, did not show effects similar to aripiprazole. The attenuation effect of aripiprazole was blocked by pretreatment with the specific serotonin 5-HT1A antagonist WAY100635. These results of aripiprazole suggest that the attenuation effect of aripiprazole was mediated by 5-HT1A receptors and imply that aripiprazole may have therapeutic value in treating drug-induced psychosis and schizophrenia.
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PMID:Aripiprazole attenuates established behavioral sensitization induced by methamphetamine. 2056 55