Relative to esketamine, arketamine possesses 4 to 5 times lower
hallucinogenic effects of racemic ketamine and that it may be responsible for the lowering of the seizure threshold seen with racemic ketamine.[7] However several subsequent studies have indicated that esketamine is more likely to induce dissociative events,[8][9] while studies in patients undergoing electroconvulsive therapy suggested that esketamine is a potent inducer of seizures.[10] Esketamine inhibits the dopamine transporter about 8-fold more potently than does arketamine, and so is about 8 times more potent as a dopamine reuptake inhibitor.[11] Arketamine and esketamine possess similar potency for interaction with the muscarinic acetylcholine receptors.[12]
Novel antidepressant
Arketamine appears to be more effective as a rapid-acting antidepressant than esketamine in
abuse potential in addition to superior antidepressant efficacy.[14]
A study conducted in mice found that ketamine's antidepressant activity is not caused by ketamine inhibiting NMDAR, but rather by sustained activation of a different glutamate receptor, the
Paradoxically, arketamine shows greater and longer-lasting rapid
mammalian target of rapamycin function) correlate closely with their affinity for it.[19][20][21] The picture is unclear however, and other mechanisms have also been implicated.[14]
Clinical development
As of November 2019, arketamine is under development for the treatment of depression under the developmental code names PCN-101 by Perception Neuroscience in the United States and HR-071603 by Jiangsu Hengrui Medicine in China.[4][5]
