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Comparison of the Analgesic Activity of Antiparkinsonian Aminoadamantane Derivatives Amantadine and Hemantane

Advances in Parkinson's Disease 2016年第3期5卷 50-60页

作者： Elena Ivanova Inga Kapitsa Elena Valdman Tatyana Voronina Laboratory of Psychopharmacology Zakusov Institute of Pharmacology Moscow Russia

The efficacy of some aminoadamantane derivatives used as neurodegeneration treatments is due to their ability to block NMDA receptors. But this mechanism of pharmacological action can also produce analgesic activity. Analgesic properties of two aminoadamantanes, amantadine (20 mg/kg) and hemantane (20 mg/kg), which were uncompetitive NMDA receptor antagonists, were assessed in rodent models of pain induced by different pain stimuli (tail-flick test, acetic twitches test in mice and formalin test in rats). Additionally, the anti-inflammatory properties of hemantane and amantadine were evaluated in mice with acetic peritonitis and in rats with hind paw edema induced by formalin injection. The results of our study demonstrate that the analgesic activity of the 1-aminoadamantane amantadine differs from the 2-aminoadamantane hemantane. The analgesic activity of amantadine administered intraperitoneally was more pronounced in the case of acute thermal pain in mice compared to hemantane, and only amantadine had a significant analgesic effect on the acute early phase of formalin pain in rats induced by the effect of the algogen on the primary sensory afferents. Hemantane was more effective than amantadine for relieving pain produced by inflammation owing to its pronounced anti-inflammatory activity: only hemantane decreased the amount of acetic twitches in mice that received drugs orally and was effective in the tonic phase of formalin pain in rats.

关键词： NMDA Receptor Antagonists tail-flick test Acetic Twitches Formalin test Exudative Inflammation

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Functional interaction between orexin and CB1 receptors in the periaqueductal gray matter on antinociceptive responses induced by stimulation of the lateral hypothalamus

Functional interaction between orexin and CB1 receptors in t...

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中国神经科学学会第十二届全国学术会议

作者： Leila Zarepour Abbas Haghparast Department of Physiology Iran University of Medical Sciences Neuroscience Research Center School of Medicine Shahid Beheshti University of Medical Sciences

Orexin receptors are found at high density in the ventrolateral periaqueductal gray matter（vl PAG）. Chemical stimulation of the lateral hypothalamus（LH） with carbachol induces antinociception in the tail-flick test, a model of acute pain. In the current study, we tried to examine the effect of TCS OX2 29 as an Ox2 r antagonist（5, 15, 50, 150 and 500 n M） microinjected into the vl PAG on LH-induced antinociception by carbachol administration（125 n M）. TCS OX2 29 dose dependently reduced carbacholinduced antinociception. In our previous study, we showed that the vl PAG CB1 receptors are involved in mediation of antinociceptive effect of carbachol. In the second set of experiments, animals were treated with carbachol 5 min after intra-vl PAG administration of 15 n M TCS OX2 29 and 1 n M AM251（as a selective CB1 receptor antagonist）, or 150 n M TCS OX2 29 and 10 n M AM251. The findings showed that the antinociceptive effect of orexin is partially mediated by activation of vl PAG Ox2 receptors. Furthermore, the administration of ineffective doses of Ox2 and CB1 receptor antagonists reduced the LHinduced antinociception. It seems that the orexinergic and cannabinoid systems in the PAG cooperate in the mediation of LH-induced antinociception.

关键词： Pain Lateral hypothalamus Periaqueductal gray Orexin-2 receptor CB1 receptor tail-flick test

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