effect of calcium channel blockers amlodipine, lacidipine and diltiazem on thermal and visceral pain in mice

ABSTRACT

The effect of the calcium channel blockers amlodipine, lacidipine and deltiazem was studied after subcutaneous [s.c.] injection in mice using the hot plate and abdominal stretching assays. In the hot-plate test of thermal pain, amlodipine [0.43 and 0.86 mg/kg], lacidipine [0.17 and 0.35 mg/kg] or deltiazem [5.2 and 10.4 mg/kg], produced a dose-related reduction in nociceptive responses. In the acetic acid-induced abdominal constrictions test of visceral pain, amlodipine, lacidipine or deltiazem at the above doses, reduced the number of abdominal constrictions dose-dependently. The inhibition of writhing response by the three drugs was reduced by co-administration of the muscarinic acetylcholine receptor antagonist atropine [1 mg/kg, s.c.], enhanced by co-administration of the alpha-1 adrenoceptor blocker prazosin [1 mg/kg, s.c.], whilst the analgesic effect of lacidipine and deltiazem was reduced by the alpha-2 adrenoceptor blocker yohimbine [5 mg/kg, s.c.]. The analgesic effect of both amlodipine and Iacidipine was unaffected, but that of deltiazem was reduced by the beta adrenoceptor antagonist propranolol [1 mg/kg, s.c.]. The non-selective opioid receptor antagonist naloxone [5 mg/kg, i.p.] enhanced the analgesic effect of amlodipine, but reduced that of deltiazem. Meanwhile, lacidipine anti-nociception was reduced by the non-selective adenosine receptor antagonist theophylline [20 mg/kg, s.c.]. These data suggest that the calcium channel antagonists amlodipine, Iacidipine or deltiazem have analgesic effects in thermal and visceral pain models in mice. Data also indicate that muscarinic acetylcholine receptors mediate at least in part the visceral analgesic effect of these drugs. The antinociceptive effect of lacidipine involves adenosine receptors. The antinociceptive effect of deltiazem involves opioid, alpha-2 and beta adrenoceptors