Mode Of Action

A lot of work has been done over the past decades regarding the modes of action of Opoids. Great emphasis has been placed on developing effective anti-nociceptive drugs that reduce the classic side effects of Opoids (E.g., dry mouth, drowsiness, nausea, respiratory depression, constipation) and also reduce the abuse and addiction potential. To this end much has been studied about the mechanisms by which Opoids potentiate pain and affect the brain. Three primary groups of Opoid receptors have been described: mu, kappa and delta (µ, ĸ, δ). These receptor classes also have several subclasses described. All of the receptors have endogenous ligands known as encephalins and endorphins. All of these receptors are found in brain and spinal cord tissue. This system of receptors and endogenous ligands appears to be intimately involved with natural modulation of pain in the body.

Signal transduction mechanisms have been described for each of the classes of receptors. The µ and δ receptors are Gi protein-linked to the inhibition of adenylylcyclase activity. Thus, binding at the µ and δ receptors will result in reduced cyclic adenosine monophosphate (cAMP) production and a resultant increase in intracellular potassium concentration and hyper-polarization of the cell membrane. There are two subdivisions of µ, namely µ1 and µ2, are thought to have a greater role in the modulation of pain and respiratory depression, respectively. The K receptors have an apparent Gi protein link to calcium channels. Agonists of these receptors produce analgesia, diuresis, sedation, and dysphoria without the strong respiratory depression and constipation observed with µ agonists. The δ receptors are not well-described, though endogenous ligand binding may predominate at this receptor class.

Table 10-2 Summary of Opoid Pharmacological Effects

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