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Titolo:
NEUROCHEMICAL EVIDENCE FOR ANTAGONISM BY OLANZAPINE OF DOPAMINE, SEROTONIN, ALPHA(1)-ADRENERGIC AND MUSCARINIC RECEPTORS IN-VIVO IN RATS
Autore:
BYMASTER FP; HEMRICKLUECKE SK; PERRY KW; FULLER RW;
Indirizzi:
ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS INDIANAPOLIS IN 46285
Titolo Testata:
Psychopharmacology
fascicolo: 1-2, volume: 124, anno: 1996,
pagine: 87 - 94
Fonte:
ISI
Lingua:
ENG
Soggetto:
ATYPICAL NEUROLEPTICS; ANTIPSYCHOTIC-DRUGS; BRAIN; METABOLISM; NEURONS; INVIVO; D2; NOREPINEPHRINE; ACETYLCHOLINE; ACCUMULATION;
Keywords:
ATYPICAL ANTIPSYCHOTIC; OLANZAPINE; DOPAMINE ANTAGONIST; DOPAMINE; SEROTONIN; MUSCARINIC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
F.P. Bymaster et al., "NEUROCHEMICAL EVIDENCE FOR ANTAGONISM BY OLANZAPINE OF DOPAMINE, SEROTONIN, ALPHA(1)-ADRENERGIC AND MUSCARINIC RECEPTORS IN-VIVO IN RATS", Psychopharmacology, 124(1-2), 1996, pp. 87-94

Abstract

The ability of the atypical antipsychotic drug candidate olanzapine to antagonize dopamine, serotonin, alpha-adrenergic and muscarinic receptors in vivo was assessed by various neurochemical measurements in rat brain. Olanzapine increased the concentrations of the dopamine metabolites DOPAC and HVA in striatum and nucleus accumbens. Olanzapine antagonized the pergolide-induced decrease of striatal DOPA concentrations in rats treated with gammabutyrolactone and NSD1015 and increased striatal 3-methoxytyramine concentrations in nomifensine-treated rats (but not after gammabutyrolactone administration), suggesting that olanzapine blocked terminal and somatodendritic autoreceptors on dopamine neurons. Inactivation of dopamine D-1 and D-2 receptors by EEDQ was antagonized by olanzapine. The ex vivo binding of the 5HT(2) radioligand [H-3]-ketanserin was inhibited by olanzapine treatment, as was quipazine-induced increases in MHPG-SO4, evidence suggesting that olanzapine antagonized 5HT(2) receptors. At higher doses, olanzapine increased the concentrations of the norepinephrine metabolite, MHPG-SO4, probably by blocking alpha(1)-adrenergic receptors. Olanzapine inhibited ex vivo binding of the muscarinic antagonist radioligand [H-3]-pirenzepine and lowered concentrations of striatal, but not hippocampal, acetylcholine levels. The findings provide evidence that olanzapine antagonized dopamine, serotonin, alpha-adrenergic and muscarinic receptors in vivo, consistent with its high affinity for these receptor sites in vitro.

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Documento generato il 29/09/20 alle ore 06:22:28