Table 1.

A Repertoire of Ketamine Targets (derived from [53]).

Target	Action	Comments	Reference
Glutamate receptor ionotropic, NMDA 3A	antagonist	blocks the open ion channel directly and through negative allosteric regulation; prevents the activation of a calcium-dependent NO synthetase, which plays a role in nociception and neurotoxicity	[59]
5-hydroxytryptamine receptor 3A	potentiator	increases voltage-gated potassium channel activity; binds at supratherapeutic doses, and is thought to increase the effects of the receptor through indirect mechanisms	[60]
α-7 nicotinic cholinergic receptor subunit	antagonist	its effects on skeletal muscle tone are not noticed unless unmasked by additional muscle relaxants; ketamine’s NMDAR antagonism additionally inhibits acetylcholine release through the receptors	[61]
Muscarinic acetylcholine receptor M1	inhibitor	primarily found in the hippocampus and the cerebral cortex	[62]
Nitric oxide synthase	indirect inhibitor	in the brain; functions through the glutamate/NO/cGMP system; may contribute to neuroprotective, sympathetic activating, and additional analgesic effects	[63]
Neurokinin 1 receptor	antagonist	through noncompetitive inhibition; possibly contributes to an analgesic effect, as this receptor modulates spinal cord nociception, but the therapeutic relevance of this interaction is not fully clear	[64]
Dopamine D2 receptor	agonist/partial agonist	specifically binds to the high-affinity state of the receptor; binding is more than 10 times weaker than that of dopamine and phencyclidine	[65]
Opioid receptors	mild agonist	binding affinity from strongest to weakest: mu > kappa > delta; related to some analgesic properties and adverse side effects, particularly with the kappa receptor	[66,67]
Sodium-dependent noradrenaline transporter	inhibitor	blocks reuptake in the heart, leading to increased chronotropy and vasoconstriction	[68]