Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors.

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Hustveit O, Maurset A, Oye I

Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors.

Pharmacol Toxicol. 1995 Dec;77(6):355-9.

PubMed ID

8835358 [ View in PubMed

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Abstract

In order to elucidate the mechanisms of action of ketamine, we have investigated the binding of the chiral forms of ketamine to opioid (mu, delta and kappa), phencyclidine, sigma and muscarinic receptors and we have performed detailed concentration-response experiments in the guinea-pig ileum preparation. The affinity ratios for the chiral forms at phencyclidine, mu and kappa receptors correlated with the potency ratio of the chiral forms in the ischaemic pain test found previously. The affinities were highest for phencyclidine receptors. The affinities for muscarinic receptors were lower than for phencyclidine receptors by a factor of about 10-20. The concentration-response experiments revealed one opioid (naloxone sensitive) and one non-opioid component. The two component are very close, which explains why other authors have reported that naloxone antagonizes the ketamine effect only partly. The concentrations of naloxone necessary to shift the opioid part of the curves indicate that ketamine is a kappa agonist in the guinea-pig ileum preparation. We conclude that the analgesic effect of ketamine in humans is most probably mediated via phencyclidine receptors, although a kappa effect can not be excluded. Binding to kappa and muscarinic receptors may contribute to the psychotomimetic side effects seen during recovery from ketamine anaesthesia.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ketamine	Delta-type opioid receptor	Protein	Humans	Unknown	Binder	Details
Ketamine	Kappa-type opioid receptor	Protein	Humans	Unknown	Agonist	Details
Ketamine	Mu-type opioid receptor	Protein	Humans	Unknown	Binder	Details
Ketamine	Muscarinic acetylcholine receptor (Protein Group)	Protein group	Humans	Unknown	Binder	Details