Detail:

        Para-Methoxyamphetamine (PMA; "Death", "Dr. Death"), also known as 4-methoxyamphetamine (4-MA), is a designer drug of the amphetamine class with serotonergic effects. Unlike other similar drugs of this family, PMA does not produce stimulant, euphoriant, or entactogen effects, and behaves more like an antidepressant in comparison, though it does have some psychedelic properties.

       PMA has been found in tablets touted as MDMA (ecstasy)although its effects are markedly different compared to those of MDMA. The consequences of such deception have often included hospitalization and death for unwitting users. PMA is commonly synthesized from anethole, the flavor compound of anise and fennel, mainly because the starting material for MDMA, safrole, has become less available due to law enforcement action, causing illicit drug manufacturers to use anethole as an alternative.

Adverse effects:

        PMA has been associated with numerous adverse reactions including death. Effects of PMA ingestion include many effects of the hallucinogenic amphetamines including accelerated and irregular heartbeat, blurred vision, and a strong feeling of intoxication that is often unpleasant. At high doses unpleasant effects such as nausea and vomiting, severe hyperthermia and hallucinations may occur. The effects of PMA also seem to be much more unpredictable and variable between individuals than those of MDMA, and sensitive individuals may die from a dose of PMA that a less susceptible person might only be mildly affected by. While PMA alone may cause significant toxicity, the combination of PMA with MDMA has a synergistic effect that seems to be particularly hazardous. Since PMA has a slow onset of effects, several deaths have occurred where individuals have taken a pill containing PMA, followed by a pill containing MDMA some time afterwards due to thinking that the first pill was not active.

Overdose:

        PMA overdose can be a serious medical emergency that may occur at only slightly above the usual recreational dose range, especially if PMA is mixed with other stimulant drugs such as cocaine or MDMA. Characteristic symptoms are pronounced hyperthermia, tachycardia, and hypertension, along with agitation, confusion, and convulsions. PMA overdose also tends to cause hypoglycaemia and hyperkalaemia, which can help to distinguish it from MDMA overdose. Complications can sometimes include more serious symptoms such as rhabdomyolysis and cerebral hemorrhage, requiring emergency surgery. There is no specific antidote, so treatment is symptomatic, and usually includes both external cooling, and internal cooling via IV infusion of cooled saline. Benzodiazepines are used initially to control convulsions, with stronger anticonvulsants such as phenytoin or thiopental used if convulsions continue. Blood pressure can be lowered either with a combination of alpha blockers and beta blockers (or a mixed alpha/beta blocker), or with other drugs such as nifedipine or nitroprusside. Serotonin antagonists and dantrolene may be used as required. Despite the seriousness of the condition, the majority of patients survive if treatment is given in time, however, patients with a core body temperature over 40 °C at presentation tend to have a poor prognosis.

Pharmacology:

        PMA acts as a selective serotonin releasing agent (SSRA) with weak effects on dopamine and norepinephrine transporters. However, relative to MDMA, it is considerably less effective as a releaser of serotonin with properties more akin to a reuptake inhibitor in comparison. It evokes robust hyperthermia in rodents while producing only modest hyperactivity and serotonergic neurotoxicity, substantially lower than that caused by MDMA, and only at very high doses Accordingly, it is not self-administered by rodents unlike amphetamine and MDMA, and anecdotal reports by humans suggest it is not particularly euphoric at all, perhaps even dysphoric in contrast.[citation needed] PMA has also been shown to act as a potent, reversible inhibitor of the enzyme MAO-A with no significant effects on MAO-B, and the combination of this property and serotonin release is likely responsible for its high lethality potential.

       It appears that PMA elevates body temperatures dramatically; the cause of this property is suspected to be related to its ability to inhibit MAO-A and at the same time releasing large amounts of serotonin, effectively causing serotonin syndrome.Amphetamines, especially serotonergic analogues such as MDMA, are strongly contraindicated to take with MAOIs. Many amphetamines and adrenergic compounds raise body temperatures, whereas some tend to produce more euphoric activity or peripheral vasoconstriction, and may tend to favor one effect over another. It appears that PMA activates the hypothalamus much more strongly than MDMA and other drugs like ephedrine, thereby causing rapid increases in body temperature (which is the major cause of death in PMA mortalities). Many people taking PMA try to get rid of the heat by taking off their clothes, taking cold showers or wrapping themselves in wet towels, and even sometimes by shaving off their hair.

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