Mechanisms of the Relaxant Action of Ketamine on Isolated Porcine Trachealis Muscle

Abstract

Ketamine is a potent bronchodilator, but its mode of action is unclear. We have studied the effect of ketamine on the peripheral vagus nerve motor pathway of isolated porcine trachealis muscle. Postsynaptic nicotinic cholinergic receptors of the intramural ganglia were stimulated selectively with 1,1-dimethyl-4-phenyl-piperazinium iodide, post-ganglionic nerve fibres with electrical field stimulation (in the presence of hexamethonium) and muscarinic cholinergic receptors with acetylcholine (in the presence of tetrodotoxin). Ketamine 10(-4) mol litre-1 significantly shifted the concentration-response curves of acetylcholine (P < 0.02) and electrical field stimulation (P < 0.001) to the right and abolished the response to 1,1-dimethyl-4-phenyl-piperazinium iodide (P < 0.02). Ketamine also caused a concentration-dependent relaxation of muscle strips precontracted with acetylcholine. This was unaffected by propranolol. Ketamine relaxed muscle strips precontracted with potassium chloride, in the absence and presence of atropine. We conclude that ketamine interacts with the peripheral vagus nerve by decreasing the excitability of the postsynaptic nicotinic receptors of the intramural ganglia, and by affecting the muscarinic receptor, smooth muscle, or both. Beta-2 adrenoceptors are not involved in the mechanism of relaxation.

Total intravenous anesthesia combined with epidural eptazocine

“…No significant depression of respiration by ketamine [22,23], diazepam [23], droperidol [24] and eptazocine [25] in the respective clinical doses has been demonstrated. In addition, ketamine [26][27][28][29], opioids [5,30], diazepam [31], droperidol [24], and vecuronium [32] have been shown not to stimulate bronchial smooth muscle in the clinical doses used in this study, and this accounts for the lack of significant effects on respiration of our TIVA regime. In fact, a 72-yearold woman with a recent history of several complicated asthmatic attacks underwent uneventful subtotal gastrectomy under TIVA plus epidural eptazocine.…”

An evaluation of the efficacy of different doses of ketamine for treatment of catheter-related bladder discomfort in patients underwent urologic surgery: A prospective, randomized, placebo-controlled, double-blind study

“…[17] Ketamine by effect on the pre-ganglionic fibers, nicotinic receptors in the post-synaptic membrane of intramural ganglion, the muscarinic receptors, and the post-synaptic fibers can decrease the contractile response of the smooth muscles. [18] As Durieux showed, ketamine can inhibit muscarinic receptor signaling significantly. [19] Furthermore, ketamine by effect on the receptors of NMDA in the cortex of the brain can have analgesic effect.…”

Effects of ketamine on neostigmine-induced contractile and phosphatidylinositol responses of the rat trachea

“…Contreras et al [13] reported that ketamine blocked the toxic effects of neostigmine and physostigmine. Wilson et al [14] studied the effect of ketamine on the peripheral vagus nerve motor pathway of the isolated porcine trachealis muscle. They concluded that ketamine interacted with the peripheral vagus nerve by decreasing the excitability of the nicotinic ACh receptors of the parasympathetic postganglionic neurons.…”