Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors.

TLDR

N‑methyl‑D‑aspartate receptor activity is implicated in human sensory processing. The study used ketamine enantiomers to probe NMDA‑receptor‑mediated neurotransmission in humans. Both enantiomers displaced MK801 binding, with (S)-ketamine being at least four times more potent; subanesthetic doses produced sensory disturbances, reduced pain perception, and mild memory effects, confirming that NMDA‑receptor blockade underlies ketamine’s sensory‑modulating actions.

Abstract

The chiral forms of ketamine were applied as probes for N-methyl-D-aspartate receptor-mediated neurotransmission in humans. Both enantiomers, in clinically relevant concentrations, displaced [3H]dizocilpine (MK 801) from specific binding sites (phencyclidine sites) in membrane fractions of brain homogenates. (S)-Ketamine was at least 4 times as potent as (R)-ketamine in this respect. In healthy volunteers, the most obvious effect of subanesthetic doses of both enantiomers was altered sensory perception. (S)-Ketamine was 4 times as potent as (R)-ketamine in reducing pain perception and in causing auditory and visual disturbances. Both enantiomers caused proprioceptive disturbances (feelings of detachment from the body) and slightly reduced the ability to recall objects seen after administration of the drugs. The ability to recall objects seen immediately before drug exposure was unaffected. The results are in accordance with the hypothesis that inhibition of sensory perception by ketamine in subanesthetic concentrations is due to N-methyl-D-aspartate receptor blockade. It is suggested that N-methyl-D-aspartate receptor-mediated transmission is involved in the processing of sensory information in the human brain.