Morphine multiple opioid receptors

The development of acute tolerance and dependence evoked in mice by morphine can be suppressed by pretreatment with NTI. Multiple administration of either NTI or 5 NTII before and during chronic implantation with morphine pellets also substantially inhibits the development of morphine tolerance and dependence. These results suggest the use of 8 antagonists to be useful for the prevention of opioid tolerance and physical dependence without compromising the antinociceptive potency of p opioid receptor agonists (Abdelhamid et al., 1991). 

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... 

Endogenous opioid peptides (endorphins, dynor-phins, enkephalins), have been termed the brain s own morphine. Their discovery in 1972 explained why the brain has opioid receptors when there were no opioids in the body. These peptides attach to specific opioid receptors, mainly p (mu), 5 (delta) or K (kappa) located at several spinal and multiple supraspinal sites in the CNS. Opioid receptors are part of the family of G-protein-coupled receptors (see p. 91) and act to open potassium channels and prevent the opening of voltage-gated calcium channels which reduces neuronal excitability and inhibits the release of pain neurotransmitters, including substance P. 

Sdentitic studies of opioid neurotransmitters during the 1970s have uncovered a complex and subtle system that exhibited impressive diversity in terms of endogenous ligands for only three major receptors. The opioid peptide precursors were subject to complex post-translational modifications resulting in the synthesis of multiple active peptides all of them sharing the common N-terminal sequence of Tyr-Gly-Gly-Phe-(Met or Leu), which has been termed the opioid motif. Based on the results of theses studies, the endogenous opioids have been implicated in circuits involved in the control of sensation, emotion, and affect and a role has been ascribed to them in addiction, not only to opiates such as morphine or heroin, but also to alcohol. ... 

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