PMA

Para-methoxyamphetamine (PMA) is a synthetic amphetamine derivative with a methoxy group at the para position of the phenyl ring. It is a potent serotonergic stimulant that has been sold as MDMA or mixed into tablets marketed as ecstasy. PMA is associated with severe hyperthermia, seizures, cardiovascular complications and fatal poisoning. Its slow onset compared with MDMA has been a recurring factor in cases where people took more after initially feeling little effect.

Chemistry and history

PMA is a ring-substituted amphetamine. Its structure is similar to amphetamine, with a methoxy group attached at the 4-position of the aromatic ring. It is closely related to PMMA, which has an additional methyl group attached to the nitrogen. PMA is also a metabolite of PMMA.

PMA appeared on illicit drug markets as an adulterant or substitute for MDMA. It has been associated with outbreaks of poisoning in several countries since the 1990s. Forensic reports have repeatedly found it in tablets sold as ecstasy, sometimes together with MDMA or other stimulants.

Pharmacology

PMA has a strong effect on serotonin signalling. Animal studies found that it inhibits serotonin uptake and can promote serotonin release, while having a weaker effect on dopamine than MDMA. In one comparative study, PMA produced potent inhibition of serotonin uptake but did not inhibit dopamine uptake in the same way as MDMA. The authors concluded that its acute adverse effects were more likely to involve serotonergic than dopaminergic mechanisms (Differential behavioural and neurochemical effects of PMA and MDMA in rats, 2000).

This profile helps explain why PMA can produce severe toxicity without the same prominent stimulant or euphoric effects people may expect from MDMA. Its pharmacology is not simply a weaker version of MDMA.

Reported effects

Human accounts describe stimulant effects that may arrive later and be less pronounced than expected from a product sold as ecstasy. This delay can lead to repeated intake before the full effects are apparent. Reported symptoms include agitation, sweating, tremor, tachycardia and marked increases in body temperature.

Physical and neurological effects

Severe poisoning has involved hyperthermia, seizures, arrhythmias, coma and cardiovascular collapse. Hypoglycaemia and hyperkalaemia have also been reported in PMA intoxications. A retrospective hospital study found that patients with PMA poisoning experienced tachycardia, hyperthermia, coma, seizures and conduction abnormalities more frequently or severely than patients presenting after self-reported ecstasy use (PMA poisoning: clinical features and outcome, 2001).

Clinical toxicity

Fatal cases have been reported in several countries. A Norwegian case report described a teenager who developed coma, seizures and hyperthermia after exposure to PMA and PMMA, followed by cardiac arrest. The authors noted that the delayed onset of PMA effects can contribute to accidental overconsumption (PMA poisoning: a party drug with lethal effects, 2003).

Another forensic series documented three fatal cases involving PMA, including cases in which other drugs were also detected (Fatal PMA poisoning cases in Poland, 2010).

Related compounds

PMA is related to PMMA, its N-methyl analogue, and to amphetamine. It is also a metabolite of PMMA, which is important when interpreting toxicological results after exposure to either compound.