Endogenous Opiates

In the late 1970s, it was hypothesized that inhaled anesthetics may work through an action on the opiate receptor. Consistent with this hypothesis are the clinical observations and experimental findings that synthetic narcotics partially decrease the requirement for inhaled anesthetics and that the administration of naloxone, a narcotic antagonist, may partially reverse certain actions of inhaled anesthetics. However, high doses of naloxone have little or no influence on anesthetic requirement (e.g., MAC), and any antagonistic effects of naloxone probably result from a general increase in CNS excitation and not by pharmacologic competition for inhaled anesthetics at opiate receptors.^[79]

Another prediction of the opiate theory of anesthesia is that inhaled agents may release an endogenous opiate-like substance in the CNS. Data are available both to support and to refute this prediction. Nitrous oxide markedly increases proenkephalin-derived endogenous opioid peptides in canine third ventricle CSF.^[80] The lowering of halothane MAC in rats by transcranial electrical stimulation is reversed by naloxone, suggesting that release of endogenous opioids mediated the decrease in halothane requirement.^[81] In patients anesthetized with a combination of halothane and nitrous oxide^[82] or isoflurane,^[83] there is no elevation in the concentration of opioid peptides in CSF. Any contribution of the endogenous opiate system to the production of general anesthesia in humans does not appear to require the release of opioid peptides.