Norpethidine

Norpethidine (Normeperidine, Pethidine Intermediate B) is a 4-phenylpiperidine derivative that is both a metabolite of and a precursor to pethidine (meperidine).

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Norpethidine is a controlled drug because of its potential uses in manufacturing both pethidine itself and a range of N-substituted derivatives, but it has little opioid activity in its own right. Instead, norpethidine acts as a stimulant and causes convulsions.^[1][2]

Build up of norpethidine is a major complication when pethidine is used in medicine as an analgesic, as when pethidine is used in high doses^[3] or administered by intravenous infusion,^[4] norpethidine can accumulate in the body at a faster rate than it is being excreted, particularly in elderly patients^[5] or those with compromised liver or kidney function,^[6] resulting in a range of toxic effects, mainly convulsions, but also myoclonus^[7] and hyponatremia.^[8] These complications can be serious and have sometimes resulted in death.^[9]

Metabolism of pethidine to norpethidine is carried out mainly by CYP enzymes in the liver, and since the activity of these enzymes can vary between individuals, the rate and extent of norpethidine production can be difficult to predict.^[10][11]

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