Ketamine and the guinea-pig ileum: possible opiate agonist and antagonist actions and effects of peptidase inhibition.

The effects of ketamine and its interaction with naloxone were studied on the transmurally stimulated guinea-pig ileum preparation. Ketamine (at concentrations between 10(-4) and 10(-3) M) depressed the contractions of the ileum, showing a very steep log concentration-effect curve. Naloxone partially reversed the depressant effect of ketamine at slightly higher concentrations (between 10 nM and 1 microM) than those normally required to reverse opiate depression in this tissue. Naloxone did not affect pentobarbitone-induced depression, suggesting that ketamine has specific actions on opiate transmission. Phentolamine and propranolol did not affect the ketamine-induced depression, whereas acetylcholinesterase inhibition did not alter the action of naloxone on this depression. Ketamine showed some reversal effect on the depressant action of morphine and caused contractions of the morphine-tolerant ileum, suggesting that it may have opiate antagonist activity. Inhibition of peptidase enzymes by a mixture of dipeptides potentiated the depression after high-frequency stimulation of the ileum, but did not affect the action of ketamine. The results suggest that ketamine may interact with opiate mechanisms in the ileum to produce part of its depressant action and may also have some opiate antagonist activity.