Methiopropamine

Methiopropamine (MPA), also known as 1-(thiophen-2-yl)-2-methylaminopropane, is a synthetic stimulant structurally related to methamphetamine. It has a thiophene ring in place of the phenyl ring found in methamphetamine and has been sold as a research chemical since around 2010. Laboratory studies show that it inhibits dopamine and norepinephrine reuptake, while clinical reports describe cardiovascular, gastrointestinal and psychiatric adverse effects.

Chemistry and history

Methiopropamine is a thiophene-based analogue of methamphetamine. The sulfur-containing thiophene ring replaces the benzene ring, while the alpha-methylated side chain and N-methylamine are retained. The compound was first synthesised in 1942, but became more visible on online research-chemical markets decades later.

The World Health Organization reviewed methiopropamine and recommended its inclusion in Schedule II of the 1971 Convention on Psychotropic Substances, citing evidence of abuse and a lack of recognised therapeutic use (WHO critical review of methiopropamine).

Pharmacology

Methiopropamine inhibits the norepinephrine transporter (NET) and dopamine transporter (DAT). In a 2021 study, the reported IC₅₀ values were 0.47 µM at NET and 0.74 µM at DAT, while serotonin uptake was affected only at much higher concentrations. In mice, the compound reached the brain rapidly and produced psychomotor stimulation, although higher experimental exposure was required than for methamphetamine (Tuv and colleagues, 2021).

A separate mouse study reported dopaminergic changes and oxidative stress after methiopropamine exposure. These findings raise questions about potential neurotoxicity in experimental models, but do not establish permanent neurological injury in human users (Methiopropamine and dopaminergic neurotoxicity, 2019).

Reported effects

The PsychonautWiki profile of methiopropamine and reports reviewed by WHO describe stimulation, increased alertness, energy, focus and talkativeness. Other reports mention anxiety, restlessness, sweating, jaw tension and difficulty sleeping. These anecdotal accounts cannot establish a consistent experience.

Clinical toxicity

An analytically confirmed case report described a 27-year-old woman who developed palpitations, chest tightness, anxiety, nausea, vomiting and visual hallucinations after using a product sold as “Quicksilver”. Methiopropamine was detected in urine, together with smaller amounts of other substances (Acute toxicity associated with methiopropamine, 2014).

The WHO review also summarised reports of tachycardia, hypertension, agitation, hallucinations and other stimulant-related symptoms. Some reported cases involved multiple substances, so the contribution of methiopropamine could not always be isolated.

Research limitations

Although the 2021 transporter study provides a clearer account of its stimulant mechanism, human pharmacokinetic and clinical studies remain limited. The frequency of serious cardiovascular events, the risk of dependence and the long-term consequences of repeated exposure have not been established reliably.

Related compounds

Methiopropamine is related to Methamphetamine and other thiophene-based amphetamine analogues. Its thiophene ring distinguishes it from the phenyl-based amphetamines.