Quinpirole--a 5-HT receptor antagonist?
The rate of brain monoamine synthesis was estimated in the rat by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) following inhibition of cerebral aromatic amino acid decarboxylase by NSD-1015 (475 mumol/kg, i.p., 30 min before decapitation). As expected, pretreatment with reserpine, (8.2 mumol/kg, s.c., -18 h) produced a marked and statistically significant increase in the DOPA accumulation in the ventral striatum and in the neocortex, whereas only minor changes were noted in 5-HTP accumulation in the same brain areas. The administration of terguride or quinpirole (30 mumol/kg, s.c., -65 min) resulted in both cases in an antagonism of the reserpine-induced increase in the DOPA accumulation. The effect was less marked in the neocortex than in the ventral striatum, but there was no difference between the effects produced by either compound. In contrast, the two drugs produced opposite effects on the 5-HTP accumulation in the ventral striatum as well as in the neocortex. Thus, there was a decrease and an increase in the 5-HTP accumulation by terguride and quinpirole administration, respectively. Together the results suggest that, in the reserpine treated rat, both terguride and quinpirole to the same degree stimulate dopamine receptors in the ventral striatum and noradrenaline receptors in the neocortex. To the extent that serotonin receptors in these two brain areas mediate the effects on 5-HTP accumulation of terguride and quinpirole, respectively, these receptors appear differently affected by the two compounds: stimulation by terguride and blockade by quinpirole.
Department of Neuropharmacology, Astra Research Centre AB, Södertälje, Sweden.
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Ahlenius
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Hillegaart
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Wijkström
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology; D008090:Lisuride / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*
D015259:Dopamine Agents; D004873:Ergolines; D006834:Hydrazines; D011985:Receptors, Serotonin; D019257:Quinpirole; C006208:dironyl; D012701:Serotonin; D004295:Dihydroxyphenylalanine; D012110:Reserpine; C004297:3-hydroxybenzylhydrazine; D008090:Lisuride