Involvement of Peripheral Mechanism in the Verapamil-Induced Potentiation of Morphine Analgesia in Mice

Autor: Norifumi Shimizu, Shiroh Kishioka, Takehiko Maeda, Yohji Fukazawa, Yoshihiro Dake, Chizuko Yamamoto, Masanobu Ozaki, Hiroyuki Yamamoto
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Zdroj: Journal of Pharmacological Sciences, Vol 95, Iss 4, Pp 452-457 (2004)
Druh dokumentu: article
ISSN: 1347-8613
DOI: 10.1254/jphs.fp0040252
Popis: Morphine’s analgesic actions are thought to be mediated through both the central and peripheral nervous systems. L-type calcium channel blockers have been reported to potentiate the analgesic effects of morphine, but the locus of this interaction is not known. In this experiment, we examined the site of verapamil-induced potentiation of morphine analgesia in mice using the quaternary opioid receptor antagonist naloxone-methiodide (NLX-M). Subcutaneous injections of morphine increased locomotor activity and serum corticosterone level, which are mediated by the central nervous system. These central effects were not antagonized by 0.1 mg/kg of NLX-M, whereas this dose of NLX-M partially antagonized the analgesic effect of morphine. Treatment with verapamil potentiated morphine analgesia in a dose-dependent manner. The verapamil-induced potentiation of morphine analgesia was abolished by pretreatment with NLX-M (0.1 and 1 mg/kg). These findings suggest that peripheral mechanisms partially contribute to morphine analgesia and mediate the potentiation of morphine analgesia by verapamil. Keywords:: morphine, peripheral analgesia, calcium channel blocker, verapamil, naloxone-methiodide
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