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A K Al-Suwailem

Publications and source records attributed to A K Al-Suwailem.

3 recordsLinked to original sources

Ondansetron, a selective 5-HT3 antagonist, antagonizes methamphetamine-induced anorexia in mice.

Effects of some selective serotonergic (5-HT) antagonists on methamphetamine-induced anorexia were investigated in male mice. The least possible dose of methamphetamine alone that caused significant anorectic activity was 11 micromolkg(-1), i.p. (2 mgkg(-1)). Various doses of some selective serotonergic receptor antagonists were administered half an hour before the above mentioned dose of methamphetamine. Methiothepin potentiated, whereas NAN-190, methysergide, mianserin and ondansetron antagonized methamphetamine-induced anorectic activity. The least possible doses of these antagonists which modified methamphetamine-induced anorexia were as follows: methiothepin (1.1 micromolkg(-1), i.p.), NAN-190 (4.2 micromolkg(-1), i.p.), methysergide (2.1 micromolkg(-1), i.p.), mianserin (3.3 micromolkg(-1), i.p.) and ondansetron (0.003 micromolkg(-1), i.p.). The serotonergic antagonists at the above mentioned doses did not modify the food intake of animals not treated with methamphetamine, except for methiothepin, which produced a significant reduction, and mianserin, which produced a significant increase in food intake. The results of the present study indicated that the anorectic activity induced by methamphetamine is related to the interactions of methamphetamine with 5-HT receptor. Since a very small dose (0.003 micromolkg(-1)) of ondansetron (the 5-HT(3) antagonist), as compared with the other antagonists used in this study, antagonized the anorexia induced by methamphetamine, the 5-HT(3) receptor is likely to be the site for this interaction.

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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.

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Involvement of some 5-HT receptors in methamphetamine-induced locomotor activity in mice.

Effects of some selective 5-HT antagonists on methamphetamine-induced locomotor activity were investigated in male mice in order to study whether this effect of methamphetamine is selectively or at least partially, induced through stimulation of a specific serotonin receptor subtype. Methamphetamine (1.5 mg/kg, IP) produced a significant increase in locomotor activity. Methamphetamine-induced hyperactivity by the above mentioned dose was significantly antagonized by NAN-190 ( 5-HT(1A) antagonist) at a dose of 4 mg/kg, IP, methiothepin (5-HT(1B/1D) antagonist) at a dose of 0.1mg/kg, IP or mianserin ( 5-HT(2C) antagonist) at a dose of 8 mg/kg, IP. On the other hand, methysergide ( 5-HT(2A/2B) antagonist) at a dose of 1mg/kg, IP or ondansetron ( 5-HT(3) antagonist) at a dose of 0.5mg/kg, IP potentiated the methamphetamine-induced hyperactivity. None of the above mentioned doses of 5-HT antagonists altered the spontaneous activity of mice when administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the locomotor stimulant activity of methamphetamine in mice. This role is possibly mediated through direct stimulation of some 5-HT receptor subtypes. Stimulation by methamphetamine of 5-HT(1A), 5-HT(1B/1D) and/or 5-HT(2C) receptor subtypes may result in hyperactivity, whereas stimulation by methamphetamine of 5-HT(2A/2B) and/or 5-HT(3) receptor subtypes may result in decreased activity.

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