Stimulation of postsynaptic D2- dopamine receptors by B-HT 958 is revealed by co-treatment with the D1- receptor agonist SKF 38393.
The motor activity of reserpine-treated mice was used to study effects of B-HT 958 (2-amino-6-(p-chlorobenzyl)-4H-5,6,7,8-tetrahydrothiazolo-[5,4-d]- azepine) on postsynaptic dopamine and noradrenaline receptors. The motor activity was only slightly stimulated by B-HT 958 or by the D1- receptor agonist SKF 38393 but it was markedly increased by the two drugs given in combination. The effect of B-HT 958 peaked earlier following low rather than high doses. The enhanced motor activity was inhibited by the D2- receptor antagonist sulpiride or the D1- receptor antagonist SCH 23390, indicating that it was caused by stimulation of both receptor types. The results suggest that B-HT 958 stimulates postsynaptic D2- receptors in addition to D2- autoreceptors and that its blockade of postsynaptic alpha 2-adrenoceptors is of no importance for the motor activity.
Andén
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NE
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Grabowska-Andén
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M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D015259:Dopamine Agents; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D001552:Benzazepines; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; C035813:B-HT 958; D012110:Reserpine