Arketamine

Arketamine, also (R)-ketamine or R(–)-ketamine, is the (R)-(–) enantiomer of ketamine. Unlike racemic ketamine and esketamine, the S(+) enantiomer of ketamine, arketamine is less potent pharmacologically and has never been approved or marketed as an enantiopure drug for clinical use, though it is still active.

Relative to esketamine, arketamine possesses 4–5 times lower affinity for the PCP site of the NMDA receptor. In accordance, arketamine is significantly less potent than racemic ketamine and especially esketamine in terms of anesthetic, analgesic, and sedative-hypnotic effects. Racemic ketamine has weak affinity for the sigma receptor, where it acts as an agonist, whereas esketamine binds negligibly to this receptor, and so the sigma receptor activity of racemic ketamine lies in arketamine. It has been suggested that this action of arketamine may play a role in the hallucinogenic effects of racemic ketamine and that it may be responsible for the lowering of the seizure threshold seen with racemic ketamine. 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. Arketamine and esketamine possess similar potency for interaction with the muscarinic acetylcholine receptors.