Involvement of peripheral mechanism in the verapamil-induced potentiation of morphine analgesia in mice.
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.
Department of Pharmacology, Wakayama Medical University, Wakayama 641-8509, Japan.
Norifumi
N
Shimizu
Shiroh
S
Kishioka
Takehiko
T
Maeda
Yohji
Y
Fukazawa
Yoshihiro
Y
Dake
Chizuko
C
Yamamoto
Masanobu
M
Ozaki
Hiroyuki
H
Yamamoto
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020746:Calcium Channels, L-Type / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D000644:Quaternary Ammonium Compounds; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology*
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D000644:Quaternary Ammonium Compounds; D017450:Receptors, Opioid, mu; D009270:Naloxone; C041269:N-methylnaloxone; D009020:Morphine; D014700:Verapamil; D003345:Corticosterone