para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is a substituted amphetamine and monoamine releaser similar to MDMA, but with substantially higher activity as a monoaminergic neurotoxin, thought to be due to the unrestrained release of both serotonin and dopamine by a metabolite. It is used as a neurotoxin by neurobiologists to selectively kill serotonergic neurons for research purposes, in the same way that 6-hydroxydopamine is used to kill dopaminergic neurons. para-Chloroamphetamine has been detected as an apparent designer drug, along with the related 3-chloroamphetamine, which is even more potent as a releaser of dopamine and serotonin but slightly less neurotoxic. The closely related N-methylated derivative, para-chloromethamphetamine (CMA), which is metabolized to para-chloroamphetamine in vivo, has neurotoxic properties as well. Conversely, the phentermine (α-methyl) analogue chlorphentermine does not appear to be neurotoxic.

Pharmacology

PCA acts as a serotonin, norepinephrine, and dopamine releasing agent (SNDRA). Its EC50 values for monoamine release are 68.5nM for dopamine and 23.5nM for norepinephrine, whereas its EC50 value for serotonin release was not reported. PCA does not show effects like those of the selective norepinephrine and dopamine releasing agent (NDRA) amphetamine in animals but instead fully substitutes for other serotonin releasing agents like (+)-MBDB and MMAI. The findings with PCA are in contrast to those with para-fluoroamphetamine, which acts as a selective NDRA similarly to amphetamine, fully substitutes for amphetamine in animals, and fails to substitute for (+)-MBDB or MMAI.

Legal status

China

As of October 2015, 4-CA is a controlled substance in China.