Immunohistochemical analysis of the mechanism of morphine abuse and antimorphine drugs

Abstract

Morphine is the most potent opioid analgesic currently available and its use is increasing for treatment of severe pain, however, long-term morphine exposure induces physical dependence/tolearance. The mechanisms underlying the development of morphine tolerance, dependence and withdrawal manifestations are not fully understood. An exact understanding of the mechanisms may help us to develop a new strategy for the prevention of dependence, and thereby allow safe use of opiates in the clinic. Although the mechanisms underlying the phenomenon of tolerance and dependence have not been established, several biochemical changes including intracellular cAMP systems and Ca mobilization have been suggested. It has been

reported that morphine changes ionic conductances in the neurons, leading to a reduced firing of action potentials, and also inhibits adenylate cyclase by activation of inhibitory G (Gi) protein which couples opioid t -receptor, resulting in decreased cAMP

formation, However, upon repeated exposure to morphine, the adenylate cyclase activity and eAMP levels return to control levels in the tolerant state and increase above the control levels during withdrawal.