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.[1]References
- Thioperamide, the selective histamine H3 receptor antagonist, attenuates stimulant-induced locomotor activity in the mouse. Clapham, J., Kilpatrick, G.J. Eur. J. Pharmacol. (1994) [Pubmed]
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