The analgesic action of morphine‐N‐oxide

Abstract

The analgesic activity of morphine‐N‐oxide in mice and rats has been investigated and compared with that of morphine. Both morphine and morphine‐N‐oxide were more active when given subcutaneously than when given intraperitoneally. Given subcutaneously, morphine was 11–22 times more potent than morphine‐N‐oxide and when given intraperitoneally it was 39–89 times more potent. The potencies depended on the test situation and the species of animal used. In animals pretreated with amiphenazole or tacrine, the analgesic activities of morphine and morphine‐N‐oxide were increased. The potencies of these analgesic drugs given intraperitoneally were increased to a greater extent than were the potencies obtained by subcutaneous administration. A possible explanation for the increase in analgesic potency of morphine‐N‐oxide produced by pretreatment with amiphenazole or tacrine may be that morphine‐N‐oxide is rapidly inactivated in the liver and this inactivation is impaired by amiphenazole and tacrine.

Computational Study of Selected Amine and Lactam N-Oxides Including Comparisons of N-O Bond Dissociation Enthalpies with Those of Pyridine N-Oxides

“…For example, the pyrrole ring of nicotine is metabolized by flavin-containing monooxygenase 3 (FMO3) in the human liver to ( S )-nicotine 1′-N-oxide, albeit a relatively minor pathway of nicotine metabolism [ 7 , 8 , 9 ]. Similarly, morphine is metabolized to its N-oxide in the liver [ 10 ]. Trimethylamine is a metabolite derived from choline as well as carnitine.…”

Protocols for the social transfer of pain and analgesia in mice

“…However, this protocol has only been tested with (and is optimized for) the use of subcutaneously injected morphine as the analgesic agent. We have chosen subcutaneous injection as it has been previously demonstrated that morphine produces more robust analgesic effects when administered subcutaneously versus intraperitoneally ( Bianchi and Franceschini, 1954 ; Fennessy, 1968 ). However, intraperitoneal injection is also acceptable with an appropriately adjusted dose.…”

Supercritical Fluid Chromatography—Mass Spectrometry (SFC-MS) and MALDI-TOF-MS of Heterocyclic Compounds with Trivalent and Pentavalent Nitrogen in Cough Relief Medical Forms Tuxi and Cosylan

“…Morphine-N-oxide is also an analgesic [12], while other N-oxides mimic the physiccological activities of the corresponding alkaloids (I. Brondz and J. Røe, to be published) [13].…”