Intrathecal opioids, potency and lipophilicity.
To determine the relationship between potency and lipophilicity for intrathecal opioids, morphine, normorphine, pethidine and methadone were studied in an electrophysiological model in the rat. Dose-response curves were constructed for the opioid effects on C fibre evoked activity of dorsal horn nociceptive neurones following intrathecal application of each opioid, and the ED50 values were correlated with lipid solubility. A significant inverse correlation was found (P = 0.002; r = 0.998) so that the most lipid soluble drugs were the least potent. The possible mechanism of this relationship, the implications for spinal opioid use and the effect of different administration routes on the relationship between lipid solubility and potency are considered.
McQuay
Henry J
HJ
Department of Pharmacology, University College, LondonU.K. Nuffield Department of Anaesthetics, Radcliffe Infirmary, OxfordU.K. Division of Anaesthesia, Clinical Research Centre, Northwick ParkU.K.
Sullivan
Ann F
AF
Smallman
Karen
K
Dickenson
Anthony H
AH
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007278:Injections, Spinal; D008563:Membrane Lipids / Q000378:metabolism*; D008614:Meperidine / Q000008:administration & dosage / Q000493:pharmacokinetics; D008691:Methadone / Q000008:administration & dosage / Q000493:pharmacokinetics; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000493:pharmacokinetics; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu; D012995:Solubility; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D004723:Endorphins; D008563:Membrane Lipids; D009022:Morphine Derivatives; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine; D008614:Meperidine; D008691:Methadone; C010616:normorphine