Cellular Mechanisms of Action

Opioid receptors are members of the G protein super-family of receptors. Drug-induced interaction with these receptors is associated with a decrease in activation of the enzyme adenylyl cyclase and a subsequent decrease in cyclic adenosine monophosphate (cAMP) levels in the cell. Binding of opioids to their receptors produces a decrease in calcium entry to cells by decreasing the phosphorylation of the voltage operating calcium channels and allows for increased time for the channels to remain closed. In addition, activation of opi-oid receptors leads to potassium efflux, and the resultant hyperpolarization limits the entry of calcium to the cell by increasing the negative charge of the membrane to levels at which these calcium channels fail to activate. The net result of the cellular decrease in calcium is a decrease in the release of dopamine, serotonin, and nociceptive peptides, such as substance P, resulting in blockage of nociceptive transmission.

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