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Published on: November 21, 2012
NAN-190, a possible specific antagonist for methamphetamine
O T Ginawi1, A A Al-Majed, A K Al-Suwailem
1Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. otginawi@hotmail.com
Abstract:
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.
Insights
NAN-190, a 5-HT(1A) receptor antagonist, effectively blocked methamphetamine's effects on mouse behavior, including hyperactivity, appetite loss, and temperature changes. This suggests a role for serotonin in mediating methamphetamine's actions.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
Background:
- Methamphetamine exerts diverse effects, including locomotor stimulation, anorexia, analgesia, and hyperthermia.
- Serotonergic (5-HT) pathways are implicated in modulating these methamphetamine-induced effects, alongside catecholaminergic systems.
Purpose of the Study:
- To investigate the role of the 5-HT(1A) receptor in mediating methamphetamine's effects.
- To evaluate NAN-190, a selective 5-HT(1A) receptor antagonist, as a potential blocker of methamphetamine's actions.
Main Methods:
- Male mice were administered methamphetamine and NAN-190 (a 5-HT(1A) receptor antagonist) via intraperitoneal injection.
- Behavioral assessments included locomotor activity, food intake, body temperature, and antinociception (writhing test).
Main Results:
- NAN-190 significantly antagonized methamphetamine-induced locomotor activity, anorexia, and hyperthermia in mice.
- NAN-190 also antagonized the antinociceptive effect of methamphetamine in the writhing test.
- NAN-190 alone did not alter locomotor activity, food intake, body temperature, or antinociception.
Conclusions:
- The findings suggest a significant role for serotonergic mechanisms, specifically involving the 5-HT(1A) receptor, in mediating methamphetamine's effects.
- NAN-190 demonstrates potential as an antagonist for methamphetamine, highlighting the involvement of 5-HT(1A) receptors in methamphetamine's complex pharmacology.
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