Voltage-gated calcium channel blockers as potential analgesics for humans and animals

Several distinct groups of voltage-dependent calcium channels (i.e. L-, N-, P-, Q-, R- and T types) play important roles in various neuronal activities, including the control of neurotransmitter release, membrane excitability, and gene expression. At the same time the functional role of L-type calcium channels were confirmed in the regulation of pain sensitivity, mu, and kappa-opioid analgesia mechanisms and expression of tolerence. Specific voltage-gated calcium channel antagonists 1, 4 dihydropyridine (nifedipine, nimodipine, lercanidipine), phenylethylalkylamine (verapamil) benzodiazepine (diltiazem) and other (cinnarizine, prenylamine) pre-treatments significantly fortified the analgesia produced by opioid receptor agonists (morphine, heroine, phencyclidine, U50, 488H, etc.), and not only completely inhibited the development of tolerance to analgesic response but also significantly strengthened it (supersensitivity). The action of Ca2+ channel antagonists may not be directed at the opioid receptor, but be related to the central role of Ca2+ in pain transmission pathways of the central nervous system. Another suggestion is that calcium channel antagonists increase the concentration of metabolite analgesics which have an agonistic function and their time spent in the brain.