Multiple analgesic receptors

The fact that 6-opioid receptors act at spinal and supraspinal sites increases the possibility that, like morphine, 6-opioid agonists may exhibit a synergistic interaction between the spinal and supraspinal sites of action. It has been clearly established that the concurrent administration of ICV and ITH morphine results in a multiplicative antinociceptive interaction [130,131]. It is this supraspinal/spinal multiplicative nature of morphine and its clinical analgesic utility at tolerable doses. Early studies with mice indicated only... 

The concept of multiple uptake modes of ligand-receptor interaction arose from studies of acyclic analgesics of the basic anilide type 34 and was first clearly delineated by Portoghese.(71) These anilides differ from the general... 

As we shall see later, there is not one single type of analgesic receptor, but several. Multiple receptors are common. We have already seen in Chapter 11 that there are two types of acetylcholine receptor—the nicotinic and muscarinic. 

The authors proposed that MDAN-21 (46b) having a longer spacer could bridge the p and 5 receptors in multiple modes and that binding by MDAN-19 (46a) with a shorter linker would be less efficient than that by MDAN-21 (46b). As a result, the acute analgesic potency of 46a would be affected by treatment with NTI. 

Tramadol is a synthetic, centrally acting analgesic with multiple mechanisms of action. The drug is a p opioid receptor agonist, with the active metabohte (+)-0-desmethyltramadol [(-i-)-Ml] being the major contributor to its action at p opioid receptors. The enantiomers of tramadol also act synergistically by different mechanisms to inhibit pain transmission the (-i-)-enantiomer inhibits neuronal reuptake of serotonin and the (-)-enantiomer inhibits neuronal reuptake of noradrenaline [1,2]. 

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