Agmatine potentiates the analgesic effect of morphine by an alpha(2)-adrenoceptor-mediated mechanism in mice.
The effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and a combination of agmatine and morphine on tail-flick test have been investigated in mice. Adult male Swiss-Webster mice were used in the study. Agmatine (10, 20 and 40 mg/kg), clonidine (0.15 mg/kg), yohimbine (0.625 and 1.25 mg/kg), or saline were injected into mice intraperitoneally. Morphine (1 and 2 mg/kg) was given subcutaneously. Agmatine alone did not produce any significant change on radiant tail-flick latencies, but it potentiated significantly and dose-dependently morphine-induced (1 mg/kg) analgesia. The potentiating effect of agmatine (40 mg/kg) on morphine-induced analgesia was blocked completely by yohimbine (0.625 mg/kg), a selective alpha(2)-adrenoceptor antagonist, pretreatment. Clonidine (0.15 mg/kg), an alpha(2-)adrenergic receptor agonist, caused a significant increase of the tail-flick latencies of the mice. Yohimbine (0.625 mg/kg) also blocked clonidine-induced analgesia. In addition, yohimbine (0.625 mg/kg) was ineffective on the tail-flick test and did not produce any significant change on the morphine-induced analgesia. Our results indicate that cotreatment of agmatine with morphine produces antinociceptive enhancement via an alpha(2-)adrenergic receptor-mediated mechanism and agmatine-morphine combination may be an effective therapeutic strategy for medical treatment of pain.
Yeşilyurt
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Psychopharmacology Research Unit, Department of Medical Pharmacology, Faculty of Medicine, Gülhane Military Medical Academy, Ankara, Turkey.
Uzbay
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000701:Analgesics, Opioid; D004338:Drug Combinations; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D000376:Agmatine; D009020:Morphine