Opiate action

Complete C-fibre inhibitions can be produced under normal conditions but opiates do not always produce a complete analgesia in some clinical situations, especially when the pain arises from nerve damage. Reasons for this are suspected to be excessive NMDA-mediated activity which is hard to inhibit and the mobilisation of cholecysto-kinin in the spinal cord which can act as a physiological antagonist of opiate actions. The idea that pre-emptive analgesia aids post-operative pain relief by preventing the pain-induced activation of these systems is becoming popular. 

There are other important sites of opiate actions located in the 5-HT and noradrenergic nuclei of the brainstem and midbrain including the raphe nuclei, the periaquaductal... 

Kim HS, Iyengar S and Wood P (1986). Opiate actions on mesocortical dopamine metabolism in the rat. Life Sciences, 39, 2033-2036. 

Massotte D, Kieffer BL. A molecular basis for opiate action. Essays Biochem 1998 33 65-77. 

Lightman SL, Iversen LL, Forsling ML (1982) Dopamine and [D-ALA2, D-LEU5]enkephalin inhibit the electrically stimulated neurohypophyseal release of vasopressin in vitro evidence for calcium-dependent opiate action. J Neurosci 2 78-81. 

Gold MS, Byck R, Sweeney DR, Kleber HD. Endorphin-locus coeruleus connection mediates opiate action and withdrawal. Biomedicine 1979 30(1) 1. ... 

Distribution, Metabolism, and Excretion Mechanisms of Opiate Action Discovery of Endorphins What Do Endorphins Do ... 

Considerable evidence implicates calcium ion in opiate action. The pharmacologic and neurochemical data include ... 

Numerous possible mechanisms of action at the biochemical level have been proposed, in order to explain the effects of opiates. In recent years the possibility that Ca + disposition is an important underlying site of opiate action has attracted widespread interest. This is particularly so in view of the fact that Ca + is involved in numerous aspects of neuronal function, a number of which are also known to be affected by opiates, and in particular, neurotransmitter release. The concept that Ca + represents a general site of opiate action has therefore arisen as a possible explanation for the varied behavioral and biochemical effects of these drugs. 

The reports of Ca + involvement in opiate actions have lead to numerous examinations of narcotic effects on Ca +... 

Figure 1. Postulated role of Ca2 in acute opiate action.

There is considerable evidence to support the supposition that cerebroside sulfate might participate in opiate action. The data have been derived not only from in vitro experiments but in vivo ones as well and these papers have been cited and... 

Because both adenylate cyclase and guanylate cyclase appear to be Ca -dependent enzymes acting probably via CDR proteins (98,99), several investigators examined the possibility that opiate actions on these enzymes are related to changes in Ca + metabolism. Thus it has been shown that Ca + must be... 

This is especially true since a number of Ca2+-dependent effects are known to be susceptible to opiate action. The picture is further complicated by the possibility that in some cases opiate effects may not involve Ca +, while in the instances where opiate-Ca + interactions can be demonstrated, the effects on Ca + may be either directly related to drug action or may be the indirect consequence of other opiate actions such as effects on body temperature, pH or oxygen tension. 

Alternatively, it may be argued that the opiate induced changes in Ca + flux, may be secondary to altered neuronal activity caused by other more important opiate actions which do not directly involve Ca + metabolism. Similarly, it may be that while Ca + has often been observed to antagonize opiate effects, this only indicates that the Ca + can alter levels of neuronal activity but does not prove a direct effect of opiates on Ca + Since these two differing interpretations may be placed on much of the data, it would seem that an important objective for future work in this field is to instigate research which will effectively demonstrate whether or not opiate effects are being produced as a direct consequence of drug effects on Ca +. 

Paul D, Pasternak GW. Differential blockade by naloxonazine of two mu opiate actions analgesia and inhibition of gastrointestinal transit. Eur J Pharmacol 1988 149 403-404. 

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