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Journal of Pharmacology and Experimental Therapeutics

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Abstract

The central cholinergic system has a role in the antinociception induced in rodents and guinea pigs by the antimigraine drug sumatriptan.

C Ghelardini, N Galeotti, M Figini, A Imperato, M Nicolodi, F Sicuteri, G L Gessa and A Bartolini
Journal of Pharmacology and Experimental Therapeutics November 1996, 279 (2) 884-890;
C Ghelardini
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N Galeotti
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M Figini
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A Imperato
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M Nicolodi
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F Sicuteri
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G L Gessa
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A Bartolini
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Abstract

The antinociceptive effect of the antimigraine drug sumatriptan was assessed in mice and rats (hot-plate, abdominal constriction and paw-pressure tests) and in guinea pigs (paw-pressure test). The ACh extracellular concentration also was detected in the hippocampus of freely moving rats by microdialysis experiments. Antinociception was induced by sumatriptan administered both parenterally (5-10 mg.kg-1 i.v.; 10-30 mg.kg-1 i.p.) and i.c.v. (50-100 micrograms per mouse). Sumatriptan antinociception was potentiated by physostigmine (0.05 mg.kg-1 i.p.) and was prevented by the muscarinic antagonist atropine (5 mg.kg-1 i.p.), the ACh depletor HC-3 (1 micrograms per mouse i.c.v.) and the 5-hydroxytryptamine1A antagonist 1-(2-methoxyphenyl)-4-[4-(2 phthalimido)butyl] piperazine (0.5 mg.kg-1 i.p.). Naloxone, 3-aminopropyl-diethoxy-methyl-phosphinc acid, 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino) ethyl ester and reserpine, administered in doses suitable for blocking analgesi induced by morphine, baclofen, 5-hydroxytryptamine4 agonist and clomipramine, respectively, did not modify sumatriptan antinociception. Sumatriptan, administered in the range of antinociceptive doses, was able to increase the level of ACh present in extracellular hippocampal space. On the basis of these findings we can deduce that sumatriptan was able to induce antinociception by increasing cholinergic activation in the CNS. Such activation, as indicated by the antagonism exerted by 1-(2-methoxyl-phenyl)-4-[4-(2 pethalimido)butyl]piperazine, may depend on stimulation of 5-hydroxytryptamine1A autoreceptors. It remains to be clarified whether the antimigraine activity of sumatriptan in humans is totally dependent on cranial vessel vasoconstriction of whether its central cholinergic antinociception also plays a role.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 279, Issue 2
1 Nov 1996
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Abstract

The central cholinergic system has a role in the antinociception induced in rodents and guinea pigs by the antimigraine drug sumatriptan.

C Ghelardini, N Galeotti, M Figini, A Imperato, M Nicolodi, F Sicuteri, G L Gessa and A Bartolini
Journal of Pharmacology and Experimental Therapeutics November 1, 1996, 279 (2) 884-890;

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Abstract

The central cholinergic system has a role in the antinociception induced in rodents and guinea pigs by the antimigraine drug sumatriptan.

C Ghelardini, N Galeotti, M Figini, A Imperato, M Nicolodi, F Sicuteri, G L Gessa and A Bartolini
Journal of Pharmacology and Experimental Therapeutics November 1, 1996, 279 (2) 884-890;
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