Naloxone: Difference between revisions
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'''Naloxone''' is a [[drug]] that acts as an [[opiate]] [[antagonist]]<ref name=Pinel1997>Pinel, J. P. J. (1997). ''Biopsychology'' (3rd ed.). Toronto: Allyn & Bacon.</ref>. It has a high affinity for the | '''Naloxone''' is a [[drug]] that acts as an [[opiate]] [[antagonist]]<ref name=Pinel1997>Pinel, J. P. J. (1997). ''Biopsychology'' (3rd ed.). Toronto: Allyn & Bacon.</ref>. It has a high affinity for the [[receptor]]s that serve the body's [[endogenous]] opiates, or [[exogenous]] drugs like [[morphine]] or [[heroin]]. | ||
The endogenous opioid systems comprise three major families: the enkephalins, leu-enkephalin and met-enkephalin; the endorphins, particularly beta-endorphin, and the dynorphins; these families are encoded by separate genes that code for large precursor molecules (pro-opiomelanocortin (POMC); proenkephalin and prodynorphin respectively) which are cleaved enzymatically to produce the relevant active opioid peptide. These endogenous opioids act at three large classes of G-protein coupled receptors - the mu receptor (at which morphine binds with very high affinity; the delta receptor (at which leu-enkephalin is the endogenous ligand) and the kappa receptor (at which dynorphins bind with high affinity). POMC is produced only by subpopulations of neurones in the [[arcuate nucleus]] and caudal brainstem; dynorphin is expressed by many populations including the [[vasopressin]] cells of the [[supraoptic nucleus]] and [[paraventricular nucleus]] and by neurones in the arcuate nucleus. Enkephalins are produced by many neuronal populations. Leu-enkephalin can also be produced by cleavage of prodynorphin. | |||
Naloxone binds to mu receptors with very high affinity but is less potent at kappa receptors and still less potent at delta receptors; it is thus (at low doses) a relatively selective mu antagonist. | |||
Interest in the addictive properties of opiates has stimulated research into naloxone, which has been associated with immediate withdrawal symptoms in users of [[heroin]]. Naloxone may counter the behavioral suppression of opiates (e.g. the euphoria and lethargy following [[morphine]] injection) by its competition with opiates at mu receptors. It is also possible that naloxone itself exerts some behavioral influence, either in the form of general activity enhancement or as a suppressor of behavior. Experiments with the [[hamster]]<ref name=Schnur1986>Schnur, P.; Raigoza, V. P. Effects of naloxone on morphine induced sedation and hyperactivity in the hamster. ''Pharmacol. Biochem. Behav.'' 24:849-854; 1986.</ref> suggest that naloxone injected before [[morphine]] can drive activity levels even above those of [[saline]] controls. But other research on naloxone has shown that it, like morphine, may suppress some behaviors, e.g. sexual behavior in male [[rat]]s<ref name=Miller1987>Miller, R. L.; Baum, J. Naloxone inhibits mating and conditioned place preference for an estrous female in male rats soon after castration. ''Pharmacol. Biochem. Behav.'' 26:781-789; 1987.</ref>. In order for naloxone to depress activity it appears to be necessary that it be injected at relatively high doses (e.g. 10 mg/kg and above in rats), indicating that these effects are not exerted at mu receptors but more probably at kappa receptors. <ref name=Babbini1972>Babbini, M.; Davis, W. M. Time-dose relationships for locomotor activity effects of morphine after acute or repeated treatment. ''Br. J. Pharmac.'' 46:213-224; 1972.</ref>. | |||
==References== | ==References== | ||
<references/> | <references/> | ||
Revision as of 03:19, 7 March 2008
Naloxone is a drug that acts as an opiate antagonist[1]. It has a high affinity for the receptors that serve the body's endogenous opiates, or exogenous drugs like morphine or heroin.
The endogenous opioid systems comprise three major families: the enkephalins, leu-enkephalin and met-enkephalin; the endorphins, particularly beta-endorphin, and the dynorphins; these families are encoded by separate genes that code for large precursor molecules (pro-opiomelanocortin (POMC); proenkephalin and prodynorphin respectively) which are cleaved enzymatically to produce the relevant active opioid peptide. These endogenous opioids act at three large classes of G-protein coupled receptors - the mu receptor (at which morphine binds with very high affinity; the delta receptor (at which leu-enkephalin is the endogenous ligand) and the kappa receptor (at which dynorphins bind with high affinity). POMC is produced only by subpopulations of neurones in the arcuate nucleus and caudal brainstem; dynorphin is expressed by many populations including the vasopressin cells of the supraoptic nucleus and paraventricular nucleus and by neurones in the arcuate nucleus. Enkephalins are produced by many neuronal populations. Leu-enkephalin can also be produced by cleavage of prodynorphin.
Naloxone binds to mu receptors with very high affinity but is less potent at kappa receptors and still less potent at delta receptors; it is thus (at low doses) a relatively selective mu antagonist.
Interest in the addictive properties of opiates has stimulated research into naloxone, which has been associated with immediate withdrawal symptoms in users of heroin. Naloxone may counter the behavioral suppression of opiates (e.g. the euphoria and lethargy following morphine injection) by its competition with opiates at mu receptors. It is also possible that naloxone itself exerts some behavioral influence, either in the form of general activity enhancement or as a suppressor of behavior. Experiments with the hamster[2] suggest that naloxone injected before morphine can drive activity levels even above those of saline controls. But other research on naloxone has shown that it, like morphine, may suppress some behaviors, e.g. sexual behavior in male rats[3]. In order for naloxone to depress activity it appears to be necessary that it be injected at relatively high doses (e.g. 10 mg/kg and above in rats), indicating that these effects are not exerted at mu receptors but more probably at kappa receptors. [4].
References
- ↑ Pinel, J. P. J. (1997). Biopsychology (3rd ed.). Toronto: Allyn & Bacon.
- ↑ Schnur, P.; Raigoza, V. P. Effects of naloxone on morphine induced sedation and hyperactivity in the hamster. Pharmacol. Biochem. Behav. 24:849-854; 1986.
- ↑ Miller, R. L.; Baum, J. Naloxone inhibits mating and conditioned place preference for an estrous female in male rats soon after castration. Pharmacol. Biochem. Behav. 26:781-789; 1987.
- ↑ Babbini, M.; Davis, W. M. Time-dose relationships for locomotor activity effects of morphine after acute or repeated treatment. Br. J. Pharmac. 46:213-224; 1972.