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Pethidine (also called meperidine, brand name Demerol) is a synthetic opioid used for moderate to severe pain, though it has fallen out of favor. It is a mu-opioid agonist giving pain relief, euphoria and sedation, but it also has serotonergic activity and a toxic metabolite, normeperidine, that can build up and cause seizures. It carries a hard rule against combining with MAOIs; naloxone reverses the opioid effects.
- Pain relief
- Euphoria
- Sedation
- Respiratory depression
- Seizures from normeperidine buildup
- Serotonin toxicity with MAOIs or serotonergic drugs
- Dependence and withdrawal
Mechanism
Pethidine is a synthetic phenylpiperidine opioid and an at the mu-opioid receptor, producing analgesia, euphoria, sedation and respiratory depression. Unlike morphine-type opioids it also has notable serotonergic activity (it blocks reuptake), which is why it can trigger serotonin toxicity with serotonergic drugs. It is broken down into normeperidine, a neurotoxic that accumulates with repeated dosing and lowers the seizure threshold.
receptor fingerprint
Mu-opioid receptorAgonist
transporter (SERT)Reuptake inhibitor
Safetyrisks and cautions, not medical advice
Pethidine causes respiratory depression like other opioids and is deadly combined with other depressants such as benzodiazepines and alcohol. Its serotonergic activity makes combining it with MAOIs especially dangerous, capable of causing life-threatening serotonin toxicity, and caution is needed with other serotonergic drugs. Its metabolite normeperidine builds up with repeated or high dosing and can cause tremors and seizures. Naloxone reverses the opioid effects. Not medical advice.
Interactionsdocumented pairs only, not exhaustive
Pethidine, known as meperidine in the United States, carries the most notorious opioid interaction in pharmacology. With a monoamine oxidase inhibitor it can produce an excitatory reaction of agitation, rigidity, hyperthermia, seizures and death, or a depressive one with severe respiratory depression, hypotension and coma. The mechanism is pethidine's serotonin reuptake inhibition, a property morphine lacks; the combination is contraindicated within two weeks of an MAOI. That same serotonergic activity makes serotonin syndrome possible with SSRIs, SNRIs, linezolid and triptans.
Metabolism shapes the second hazard. Pethidine is demethylated by CYP3A4 and CYP2B6 to normeperidine, a neurotoxic metabolite with a much longer half-life that accumulates in renal impairment and causes tremor, myoclonus and seizures. Naloxone does not reverse it, and enzyme inducers such as phenobarbital, phenytoin and rifampin push more drug down that route. Benzodiazepines and other central depressants add respiratory depression on top.
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Subjective profileweighing the evidence above
Outclassed and best avoided. Its metabolite accumulates with repeated or high dosing and causes tremor and seizures, it is absolutely off limits with MAOIs because of serotonin toxicity, and it carries every ordinary opioid risk on top. Other opioids do the same job without the seizure liability.
Resources
No suppliers are provided for compounds like this. This entry is here for reference.
Research
- 1.Meperidine: a critical review.
- 2.Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects.
2 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Why is pethidine used less now?
Its toxic metabolite normeperidine can accumulate and cause seizures, and its serotonergic activity creates dangerous interactions, so safer opioids are usually preferred.
Why is it dangerous with MAOIs?
Pethidine blocks serotonin reuptake, and combined with an MAOI this can trigger life-threatening serotonin toxicity; it is a hard combination to avoid.
Does naloxone reverse it?
Naloxone reverses the opioid effects, but it does not treat the seizure risk from normeperidine buildup.
Adverse effects
- Respiratory depression
- Seizures from normeperidine buildup
- Serotonin toxicity with MAOIs or serotonergic drugs
- Dependence and withdrawal