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.