Ca2+-channel antagonist

Butyrophenones Butyrylcholinesterase C2 Domain C Kinase C-reactive Protein Ca2+-ATPase Ca2+-binding Proteins Ca2+ Channel Ca2+ Channel Antagonists Ca2+ Channel Blockers... 

Enhancement of opioid mediated antinociception by L-type Ca2+ channel antagonists... 

Table 1 Antinociceptive activity of L-type Ca2+ channel antagonists in specified pharmacological assays.

We reevaluated these experiments to determine the relationship between antinociceptive efficacy and possible side-effects which were only poorly reported in the literature. The first approach - application of L-type Ca2+ channel antagonists alone - was not convincing. The antinociceptive effect was rather poor and, since L-type Ca2+ channel antagonists have been used for the treatment of hypertension for many years, side-effects like hypotension are to be expected. 

The second approach however - enhancement of opioid antinociception by L-type Ca2+ channel antagonists - offers the possibility for very effective antinociception with a reduced spectrum of side effects due to the opioid-sparing effect (Reimann (Grunenthal GmbH), 1998). 

High doses of the N-type VDCC inhibitors produce characteristic shaking behavior, serpent-like tail movements, and impaired coordination. At antinociceptive doses however there is no significant motor effect although some of the N-type Ca2 channel antagonists produce tail movements (Malmberg and Yaksh, 1994). 

Catterall, W.A. and Striessnig, J. Receptor sites for Ca2+ channel antagonist, Trends Pharmacol. Sci. 1992, 13, 256-262. 

Michaluk, J., Karolewicz, B., Antkiewicz-Michaluk, L., Ventulani, J. Effects of various Ca2 channel antagonists on morphine analgesia, tolerance and dependence, and on blood pressure in the rat, Eur. J. Pharmacol. 1998, 352, 189-197. 

TABLE I Ca2+-Channel Antagonist Activities in Smooth Muscle Preparations (9, 12)... 

Structure-activity data are quite restricted for other classes of Ca2+ channel antagonists. For a limited series of verapamil derivatives carrying ring substituents (II), negative inotropic activity depends upon both electronic and steric properties of the substituent (52f53),... 

Amlodipine is a calcium-channel-blocking agent, which is indicated in the treatment of hypertension, chronic stable angina, and vasospastic (Prinzmetal or variant) angina. The ten Ca2+ channel antagonists that are in chnical use in the... 

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