Analgesic action of loperamide, an opioid agonist, and its blocking action on voltage-dependent Ca2+ channels.
We investigated the relationship between the antinociceptive effect of the opiate agonist loperamide at the spinal level and its inhibitory effect on calcium influx. Intrathecal administration of loperamide showed a significant antinociceptive effect in the formalin test, which was not prevented by naloxone. On the other hand, no significant effects were observed by nicardipine, an L-type specific blocker, or by BAY K8644, an L-type specific agonist, suggesting no significant role of L-type calcium channels in nociceptive signal transduction. Loperamide suppressed the calcium influx in dorsal root ganglion neurons. As the antinociceptive effect of loperamide was not affected by naloxone or other calcium channel blocking toxins, and loperamide showed a direct inhibitory effect on calcium-influx, the analgesic effect of intrathecally injected loperamide might be due to its blockade of the voltage-dependent calcium channels at the terminals of the primary afferent fibers.
Hagiwara
Kunie
K
Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryomachi Aobaku, Sendai 980-8575, Japan.
Nakagawasai
Osamu
O
Murata
Atsunobu
A
Yamadera
Fumihiro
F
Miyoshi
Ichiro
I
Tan-No
Koichi
K
Tadano
Takeshi
T
Yanagisawa
Teruyuki
T
Iijima
Toshihiko
T
Murakami
Manabu
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005110:Extracellular Space / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D008139:Loperamide / Q000494:pharmacology*; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology
D000700:Analgesics; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005456:Fluorescent Dyes; D009292:Narcotic Antagonists; D009270:Naloxone; D011189:Potassium Chloride; D008139:Loperamide; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D016257:Fura-2