Dopamine receptor mediated hypothermic action of B-HT 920 in rats.
The hypothermic action of the thiazoloazepine derivative B-HT 920, an alpha 2-adrenoceptor agonist has been investigated in rats. B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)-azepine dihydrochloride) (0.25-1.0 mg kg-1 i.p.) induced a dose-dependent hypothermia. This peak effect was seen within 60-90 min and lasted up to 120 min. Its action was potentiated by the selective D1-dopamine agonist SKF 38393 and inhibited by the D2-antagonists haloperidol (1 mg kg-1) and sulpiride (100 mg kg-1). The hypothermic action of B-HT 920 was centrally mediated; i.c.v. administration of 10 micrograms produced a significant fall in rectal temperature which was sensitive to blockade by haloperidol. B-HT 920 also potentiated the hypothermic action of apomorphine (0.1 and 0.5 mg kg-1) in a haloperidol sensitive manner. Reserpine (5 mg kg-1 i.p.) pretreatment reduced the hypothermic response of B-HT 920 (0.5 mg kg-1) but sensitized the response due to the combination of B-HT 920 (0.5 mg kg-1) and apomorphine (0.1 mg kg-1). Neither the selective alpha 2-adrenoceptor antagonists, yohimbine (1 mg kg-1) or idazoxan (1 mg kg-1), the histamine antagonist mepyramine (10 mg kg-1) nor the 5-HT antagonist cyproheptadine (5 mg kg-1) inhibited B-HT 920-induced hypothermia. Similarly, the selective alpha 1-antagonist prazosin (1 mg kg-1) and the beta-antagonist propranolol (10 mg kg-1) failed to modify the hypothermic action of B-HT 920. These observations demonstrated hypothermia induced by B-HT 920 is mediated by postsynaptic D2-receptors and D1- and D2-receptor interplay is essential for the full expression of hypothermia in rats.
Verma
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Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D012110:Reserpine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C024763:talipexole; D012110:Reserpine; D006220:Haloperidol; D001058:Apomorphine