Sun28November0440PM 35

Ketamine hydrochloride is a phencyclidine derivative used to induce a state of dissociative anaesthesia.

A standard formulation of ketamine is administered to a patient and serial samples of plasma are subjected to gas-liquid chromatography.

Which of the following compounds subsequently measured in plasma is the most potent as an anaesthetic agent?

(Please select 1 option)

Dehydronorketamine

(S)-norketamine

(R)-ketamine

(S)-ketamine Correct

(R)-norketamine

Explanation

Most pharmacological preparations of ketamine are racemic mixtures containing equal proportions of (S)-ketamine and (R)-ketamine.

The (S) isomer alone has been shown to be twice as potent as the racemic mixture in producing anaesthesia and analgesia, and three times as potent as the single (R) isomer.

Ketamine is metabolised by hepatic microsomal cytochrome P450 enzymes. It undergoes demethylation and hydroxylation of the cyclohexanone ring to form two major metabolites, norketamine (NK) and dehydronorketamine (DHNK), which are further biotransformed to glucuronide conjugates and then excreted in the urine.

Norketamine has 20-30% of the activity of the parent compound.

Of the two isomers of norketamine, the antinociceptive properties resided primarily in the S(+) enantiomer. Antinociception was not accompanied by significant side effects. The present findings suggest that norketamine, in particular the S(+) enantiomer, might be a useful NMDA-receptor antagonist for treatment of chronic pain involving central sensitisation.

DHNK has no significant anaesthetic or analgesic properties.

Answer Statistics

1

6%

2

15%

3

18%

4

45%

5

18%

Times answered: 256