Opioids mechanisms

Benton, D. and Brain, P.F. (1988) The role of opioid mechanisms in social Interaction and attachment. In Rodgers, R.J. and Cooper, S.J., eds. Endorphins, Opiates and Behavioural Processes. New York John Wiley Sons, pp. 215-235. 

Miranda, H. F., Pelissier, T., Pinardi, G. Involvement of adrenergic, serotonergic, and opioid mechanisms in tramadol-induced antinociception in mice, Analgesia 1999, 4, 1-7. 

Tan-No, K., Taira, A., Inoue, M., Ohshima, K., Sakurada, T., Sakurada, C., Nylander, I., Demuth, H. U., Silberring, J., Terenius, L., Tadano, T., and Kisara, K. (1998). Intrathecal administration of />-hydroxymercuribenzoate or phosphoramidon/bestatin-combined induces antinociceptive effects through different opioid mechanisms. Neuropeptides 32, 411-415. 

Faden, A. I. (1992). Dynorphine increases extracellular levels of excitatory amino acids in the brain through a non-opioid mechanism.. Neurosci. 12, 425—429. 

In addition to these opioid mechanisms, nonopioid mediated pathways, e.g. serotonin, are important in pain. There is suggestion that opioid mechaiusms are more important in acute severe pain, and nonopioid mechanisms in chronic pain, and that this may be relevant to choice of drugs. 

Some of the endorphins, dynorphin and enkephalins are about as active as morphine and some have higher efficacy. The discovery of the function of natural opioid mechanisms in physiology and pathology opens up possibilities for major developments in pain management, and indeed, wider, for endogenous opioid mechanisms may play a role, e.g. in shock. 

Epibatidine, a piperidine alkaloid isolated from the frog, Epidedobates tricolor, and similar in structure to nicotine was found to be a potent analgetic (about 200x more potent than morphine) but was found to possess a non-opioid mechanism of action. Subsequent studies... 

Perhaps blocking the chemical messengers from transmitting pain information by blocking postsynaptic receptors with selective antagonists would be the best approach. This would involve non-opioids and non-opioid mechanisms, but might be the best way of eliminating side-effects. 

Gardner EL, Paredes W, Smith D, Zukin RS (1989) Facilitation of brain stimulation reward by D9-tetrahydrocannabinol is mediated by an endogenous opioid mechanism. Adv Biosci 75 671-674... 

Pleuvry BJ (2005) Opioid mechanisms and opioid drags, Anaesth Intensive Care Med 6(l) 30-34 Porter AC, Felder CC (2001) The endocannabinoid nervous system unique opportunities for therapeutic intervention, Pharmacol Ther 90 45-60... 

---