NAN-190, a possible specific antagonist for methamphetamine.
Effect of NAN-190, a selective 5-HT(1A) receptor antagonist, on methamphetamine-induced locomotor activity, anorexia, analgesia, and hyperthermia was investigated in male mice. Methamphetamine (1.5 mg/kg, i.p) produced a significant increase in locomotor activity, which was significantly antagonized by NAN-190 at a dose of 4 mg/kg, i.p. NAN-190 did not alter the antinociceptive activity of mice when it was administered alone. Methamphetamine (2 mg/kg, i.p) produced a significant decrease in food intake of mice, which were deprived of food during the previous 24h. This anorectic activity of methamphetamine was significantly antagonized by NAN-190 at a dose of 2 mg/kg, i.p. NAN-190 did not alter the food intake of mice when it was administered alone. Methamphetamine (2 mg/kg, i.p) also produced a significant increase in body temperature of mice, which was significantly antagonized by NAN-190 at a dose of 0.5 mg/kg, i.p. NAN-190 did not alter the body temperature of mice when it was administered alone. In the writhing test, methamphetamine (1 mg/kg, i.p) produced a significant antinociceptive effect in mice. This was significantly antagonized by NAN-190 at a dose of 1 mg/kg, i.p. NAN-190 did not alter the antinociceptive activity of mice when it was administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the above-studied activities of methamphetamine in mice. This role is possibly mediated through direct stimulation of the 5-HT(1A) receptor subtype. All of the above-studied activities of methamphetamine were antagonized by NAN-190, which may indicate that NAN-190 is a possible antagonist for methamphetamine.
Ginawi
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OT
Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. otginawi@hotmail.com
Al-Majed
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Al-Suwailem
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AK
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D015259:Dopamine Agents; D009292:Narcotic Antagonists; D010879:Piperazines; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D008694:Methamphetamine