Norpethidine Norpethidinic acid

Gas Chromatography-Mass Spectrometry. In plasma or serum pethidine and norpethidine, detection limit 170 pg/ml for pethidine and 500 pg/ml for norpethidine—E. L. Todd et al., J. analyt. Toxicol., 1979, 3, 256-259. In urine pethidinic and norpethidinic acids, sensitivity 500 ng/ml—C. Lindberg et al., Acta pharm. suec., 1978,15, 327-336. 

There is evidence that chlorpromazine can increase the activity of the liver microsomal enzymes so that the metabolism of pethidine to norpethidine and norpethidinic acid are increased. These metabolites are toxic and probably account for the lethargy and hypotension seen in one study. The effects of the phenothiazines on pethidine-induced respiratory depression may be related. Both the opioids and the phenothiazines are CNS depressants, and their effects may be additive. 

Pethidine is metabolized chiefly in the liver, to mainly meperidinic acid and minor metabolite norpethidine, which are conju-... 

Hyperpyrexia and hypertension have been observed with the use of pethidine and MAO inhibitors. Pethidine is the opioid most commonly associated with an adverse reaction with MAOIs. Although only a small proportion of patients taking MAOIs will react adversely to pethidine, there is no sure way of predicting those in whom the combination could produce severe, life-threatening reactions. These can present in two distinct forms. The excitatory form is characterised by sudden agitation, delirium, headache, hypotension or hypertension, rigidity, hyperpyrexia, convulsions and coma. It is possibly caused by an increase in cerebral 5-HT concentrations due to inhibition of MAO. This is potentiated by pethidine, which blocks neuronal uptake of 5-HT. The depressive form, which is frequently severe and fatal, presents as respiratoiy and cardiovascular depression and coma. It is the result of a reduced breakdown of pethidine due to the inhibition of hepatic /V-demethylase by MAOIs, leading to accumulation of pethidine. The risk of adverse reactions to pethidine may be less likely with the newer, specific MAO-A inhibitors. Interactions with other opioids, such as morphine and pentazocine, have been reported, but are less common. Other opioids appear to be safe in combination with MAOIs, with the possible exception of phenoperidine, which is metabolised to pethidine, norpethidine and pethidinic acid. 

High Pressure Liquid Chromatography. System HA—pethidine k 2.8 (tailing peak), norpethidine k 1.7 (tailing peak), pethidinic acid k 2.8 (tailing peak) system HC—pethidine k 0.55, norpethidine k 2.04. 

Morpheridine. l- 2-(Morpholinyl) Ayl]-4-phen-yl-4-piperidinecarboxytic acid ethyl ester 1-(2-morphotino-ethylh4-pheityli ouipecotic acid ethyl ester ethyl 1 -(2 -mor-pholinoethyl) 4-phenylpiperidme-4-carboxylate morpho-linoethyl norpethidine. mol wt 346 46. C... 

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