Thioperamide, the selective histamine H3 receptor antagonist, attenuates stimulant-induced locomotor activity in the mouse.
The effects of the selective histamine H3 receptor agonist (R)-alpha-methylhistamine and antagonist thioperamide on stimulant-induced locomotor activity in the mouse were examined. Amphetamine (1 mg.kg-1 s.c.), apomorphine (2 mg.kg-1 s.c.) or cocaine (5 mg.kg-1 s.c.) increased locomotor activity. Neither thioperamide (10 mg.kg-1 i.p.) nor (R)-alpha-methylhistamine (20 mg.kg-1 i.p.) affected spontaneous locomotor activity in their own right. (R)-alpha-Methylhistamine (0.3, 3 or 20 mg.kg-1 i.p.) also had no effect on amphetamine (1 mg.kg-1 s.c.)-induced locomotor activity. In contrast, thioperamide (0.2-10 mg.kg-1 i.p. or 0.3-20 micrograms i.c.v.) inhibited, in a dose-dependent manner, the hyperactivity response induced by amphetamine (1 mg.kg-1 s.c.). (R)-alpha-Methylhistamine (20 mg.kg-1 i.p.) completely reversed the inhibitory response to thioperamide (2 mg.kg-1 i.p.). Thioperamide (2 or 10 mg.kg-1 i.p.) also inhibited apomorphine (2 mg.kg-1 s.c.)- and, to a lesser extent, cocaine (5 mg.kg-1 s.c.)-induced hyperactivity. We therefore conclude that antagonism of the central histamine H3 receptor inhibits, to a varying degree, the effects of locomotor stimulants.
Department of Pharmacology (2), Glaxo Research & Development Ltd., Ware, Herts., UK.
J
J
Clapham
G J
GJ
Kilpatrick
D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017442:Histamine Agonists; D006633:Histamine Antagonists; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; C069357:alpha-methylhistamine; D000661:Amphetamine; D003042:Cocaine; C052075:thioperamide; D001058:Apomorphine