# Para-Methoxymethamphetamine

para-Methoxymethamphetamine (PMMA), also known as 4-methoxy-N-methylamphetamine (4-MMA), is a serotonergic drug of the amphetamine family related to para-methoxyamphetamine (PMA). It is the 4-methoxy analogue of methamphetamine. Little is known about the pharmacological properties, metabolism, and toxicity of PMMA; because of its structural similarity to PMA, which has known toxicity in humans, it is thought to have considerable potential to cause harmful side effects or death in overdose. In the early 2010s, a number of deaths in users of the drug MDMA were linked to misrepresented tablets and capsules of PMMA.
PMMA is a serotonin–norepinephrine releasing agent (SNRA) as well as potent monoamine oxidase inhibitor (MAOI). Its effects in humans are reputedly similar to those of PMA, but slightly more empathogenic in nature. It has a reduced tendency to produce severe hyperthermia at low dosages, but at higher dosages side effects and risk of death become similar to those of PMA.
The synthesis and effects of PMMA were described by American experimental chemist Alexander Shulgin in his book PiHKAL, where it is referred to by the name "methyl-MA", as the N-methylated form of 4-MA (PMA). Shulgin reported that PMMA produces an increase in blood pressure and in heart rate, at doses above 100 mg, but causes no psychoactive effects at these levels.

## Pharmacology
### Pharmacodynamics

PMMA is a monoamine releasing agent (MRA). The drug's EC$_{50}$Tooltip half-maximal effective concentration values for induction of monoamine release in rat brain synaptosomes have been reported for the individual enantiomers of PMMA. In the case of (S)-PMMA, they are 41 nM for serotonin, 147 nM for norepinephrine, and 1,000 nM for dopamine, whereas for (R)-PMMA, they are 134 nM for serotonin, >14,000 nM for norepinephrine, and 1,600 nM for dopamine. Hence, PMMA appears to be a serotonin–norepinephrine releasing agent (SNRA) with weak effects on dopamine. The drug has been found to strongly release serotonin and to weakly release dopamine in the brain in rodents in vivo.
In addition to its MRA activity, PMMA is a potent monoamine oxidase A (MAO-A) inhibitor. Its IC$_{50}$Tooltip half-maximal inhibitory concentration for MAO-A inhibition has been reported to be 1,700 nM. This is several-fold less potent than the related agents para-methoxyamphetamine (PMA) and 4-methylthioamphetamine (4-MTA).
Monoamine release of PMMATooltip para-methoxymethamphetamine and related agents (EC$_{50}$Tooltip Half maximal effective concentration, nM) :
| Compound | 5-HTTooltip Serotonin | NETooltip Norepinephrine | DATooltip Dopamine | Ref |
| d-Amphetamine | 698–1,765 | 6.6–7.2 | 5.8–24.8 | |
| d-Methamphetamine | 736–1,292 | 12.3–13.8 | 8.5–24.5 | |
| 2-Methoxyamphetamine | ND | 473 | 1,478 | |
| 3-Methoxyamphetamine | ND | 58.0 | 103 | |
| para-Methoxyamphetamine (PMA) | ND | 166 | 867 | |
| PMMATooltip para-Methoxymethamphetamine | ND | ND | ND | ND |
| (S)-PMMA | 41 | 147 | 1,000 | |
| (R)-PMMA | 134 | >14,000 | 1,600 | |
| 4-Methylamphetamine (4-MA) | 53.4 | 22.2 | 44.1 | |
| 4-Methylmethamphetamine (4-MMA) | 67.4 | 66.9 | 41.3 | |
| para-Chloroamphetamine (PCA) | 28.3 | 23.5–26.2 | 42.2–68.5 | |
| para-Chloromethamphetamine (PCMA) | 29.9 | 36.5 | 54.7 | |
| Methedrone (4-MeO-MC) | 120–195 | 111 | 506–881 | |
| Mephedrone (4-MMC) | 118.3–122 | 58–62.7 | 49.1–51 | |
| Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs: |||||

## Recreational use

PMMA has been found in tablets and capsules of the MDMA sold as "ecstasy". A number of deaths have been attributed to tablets sold as ecstasy that contained other substances, such as PMMA's structural analog, PMA. Death can occur when an ecstasy user believes they are consuming recreational doses of MDMA, when they are in fact consuming a lethal dose of another substance with similar effects. PMA is of particular concern because it not only causes a release of serotonin but also acts as a monoamine oxidase inhibitor (MAOI); if it is used in combination with MDMA or another MDMA-like substance, serotonin syndrome can result.
PMMA can be detected with reagent testing kits.

### Deaths

In January 2011, the Norwegian Broadcasting Corporation reported that Norway had seen 12 deaths related to PMMA over the course of six months. In March 2011, Dutch media reported that there had been four deaths in the province of Limburg since November 2010. In April 2011, Icelandic media reported the death of a young woman that may have been connected to PMMA.
In 2011, four deaths were recorded in Scotland as a result of ecstasy tablets which also contained PMMA.
In January 2012, a number of ecstasy-related deaths in Canada in the previous year were linked to PMMA overdoses. In the single year, approximately 45 exposures occurred, resulting in 21 deaths. Cases were centred primarily in Calgary and Vancouver.
In September 2012, the deaths of two men in County Cork, Ireland, have been linked to PMMA overdoses. In the same month, the death of a man in Queensland, Australia was attributed to PMMA.
In June 2013 a PMMA-related death occurred in the Dutch city of 's-Hertogenbosch. Two months later, In August 2013, another possibly PMMA-related death occurred in the nearby town of Sliedrecht.
In January 2015 in the UK four people died, suspected of taking ecstasy containing PMMA. In the same month, in Sweden, another man died from ecstasy laced with PMMA.
In May 2015 a young woman died in Dublin, Ireland, after taking what is suspected to be PMMA.
In April 2016 four young Argentines and one Uruguayan died during a massive rave called "Time Warp" in Buenos Aires and five more were hospitalized. PMMA was found in their bodies.

## Legal status
### United States

On June 25, 2021, the DEA finalized a rule placing PMMA on the Controlled Substance Act federal Schedule as a Schedule I substance effective July 26, 2021.

### United Kingdom

PMMA is controlled as a Schedule 1, Class A drug in the UK.