[3][4] PCA has also been clinically studied as an appetite suppressant and antidepressant, but findings of neurotoxicity in animals discouraged further evaluation.

[2][1][10][11] The profile of PCA is analogous to that of naphthylaminopropane (NAP; PAL-287), a highly potent and well-balanced SNDRA with only weak stimulant-like effects.

[14][15][17][18] In animals, doses of PCA of 0.5 to 5 mg/kg acutely produce a variety of behavioral and neurochemical effects thought to be due to serotonin release.

[3][19][20] Consequent enhancement of serotonergic signaling, serotonergic effects like myoclonus, the serotonin behavioral syndrome, including tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving, and reciprocal forepaw treading, inhibition of startle response sensitization, suppression of sexual behavior in females, and the head-twitch response.

[3] PCA and other SRAs like MDMA and α-ethyltryptamine (αET) produce locomotor hyperactivity in animals and this is thought to be serotonin-dependent.

[19] In line with the preceding neurochemical findings, tolerance to various of the behavioral effects of acute PCA has been found to develop.

[3] However, hypoactivity, increased defecation in the open field test, and failed acquisition of shock avoidance in the Y-maze task are all apparent.

[3] Failure of acquisition of a two-way conditioned avoidance response has been observed, and this could be completely prevented with the SRI zimelidine (see more on this below).

[3][5][19] Serotonin reuptake inhibitors (SRIs) like fluoxetine can block both the acute short-term effects and the long-term serotonergic neurotoxicity of PCA.

[3][5][19] In addition, they can be given 4 hours after PCA administration, when acute serotonin depletion has already occurred, and will still completely protect against the long-term neurotoxicity.

[3][5][19] Severe depletion of serotonin by the combination of para-chlorophenylalanine (PCPA) and reserpine substantially protects against the serotonergic neurotoxicity of PCA.

[3] It has been reported that direct intracerebroventricular injection of PCA into the brain, in contrast to peripheral administration, failed to produce serotonergic neurotoxicity.

[3] Inhibiting the metabolism of PCA does not reduce tryptophan hydroxylase inactivation, suggesting that a metabolite is not responsible for this effect.

[19] There are species differences in the neurotoxicity of PCA between rats and mice, which may help to shed light on the underlying mechanisms.

[3][5] In terms of structure–activity relationships, the α-methyl group appears to be essential for the neurotoxicity, and the α-ethyl analogue is less potent as a neurotoxin.

[5] para-Bromoamphetamine (PBA) and para-bromomethamphetamine (PBMA) show similar serotonergic neurotoxicity to PCA and PCMA.

[5] Fenfluramine and norfenfluramine, which are 3-trifluoromethylamphetamines, produce very long-lasting serotonergic neurotoxicity similarly to PCA but are slightly less active.

[5] The closely related N-methylated derivative, para-chloromethamphetamine (PCMA), which is rapidly and extensively metabolized to para-chloroamphetamine in vivo, has neurotoxic properties as well, and is only slightly less potent than PCA in this regard.

[5] Another analogue, Org 6582, in which a third ring structure has been added, is a selective serotonin reuptake inhibitor (SSRI) and no longer shows the serotonergic neurotoxicity of PCA and 6-CAT.

[3] PCA has been found to act as a relatively potent monoamine oxidase A (MAO-A) inhibitor, with an IC50Tooltip half-maximal inhibitory concentration of 1,900 to 4,000 nM.

[1][5] Analogues of PCA include para-chloromethamphetamine (PCMA/4-CMA), para-bromoamphetamine (PBA/4-BA), para-fluoroamphetamine (PFA/4-FA), para-iodoamphetamine (PIA/4-IA), 4-methylamphetamine (4-MA), meta-chloroamphetamine (MCA/4-CA), ortho-chloroamphetamine (OCA/2-CA), 3,4-dichloroamphetamine (3,4-DCA), 2,4-dichloroamphetamine (2,4-DCA), chlorphentermine, 4-chloromethcathinone (4-CMC; clephedrone), 4-chlorophenylisobutylamine (4-CAB; AEPCA), 6-chloro-2-aminotetralin (6-CAT), 5-iodo-2-aminoindane (5-IAI), and Org 6582, among others.