Flunarizine analgesia is mediated by mu-opioid receptors.
We evaluated the opioid antinociceptive mechanism of the calcium channel blocker flunarizine. Flunarizine produced a dose-dependent analgesia in the hot plate test which was antagonized by general (naloxone) and mu [beta-fualtrexamine (beta-FNA)]-opioid antagonists, indicating a role for mu receptors in flunarizine analgesia. Naltrindole (delta1 antagonist) did not affect flunarizine analgesia. A fixed subthreshold dose of flunarizine augmented mu (morphine) analgesia and blocked delta1 [enkephalin, [D-Pen2,5] (DPDPE)] analgesia. Apparently, flunarizine has mu agonistic activity and delta1 antagonist or mixed agonistic-antagonistic activity.
Weizman
R
R
Tel Aviv Community Mental Health Center, Ramat Hatayassim and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Pankova
I A
IA
Schreiber
S
S
Pick
C G
CG
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects*
D002121:Calcium Channel Blockers; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009020:Morphine; D005444:Flunarizine