Comparison of pharmacodynamic effects of the non-competitive NMDA receptor antagonists MK-801 and ketamine in pigs.
The non-competitive NMDA receptor antagonists MK-801 and ketamine were injected into pigs via chronically implanted intravenous catheters, and the animals were observed closely for alterations in general behaviour, heart rate, respiration and body temperature. MK-801 produced head shakes, sterotypies, 'psychotic' behaviour (e.g., hyperexcitation and screaming), and ketamine-like anesthetic effects in pigs at doses of 0.1-1.6 mg/kg. Almost the same behavioural pattern of effects was observed after i.v. injection of ketamine, 15mg/kg. Furthermore, both drugs reduced heart rate and increased respiration rate and body temperature. The most marked differences between MK-801 and ketamine were that MK-801 had a much longer duration of action and the catalepsy produced by MK-801 was much more pronounced. When animals were first anesthetized with pentobarbital, MK-801 did not alter the cardiovascular functions. In pigs genetically susceptible to induction of malignant hyperthermia by volatile anesthetics, MK-801 did not produce signs characteristic of fulminant malignant hyperthermia. The data show that MK-801 produces psychomotor and anesthetic effects that are almost indistinguishable from those observed after traditional dissociative anesthetics, such as phencyclidine and ketamine. With respect to the behavioural similarities between MK-801 and phencyclidine or ketamine, it seems unlikely that MK-801 will be useful clinically as an anticonvulsant or anxiolytic drug, but the data indicate that the drug may be suited as a long-acting dissociative anesthetic.
Löscher
W
W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hanover, F.R.G.
Fredow
G
G
Ganter
M
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012119:Respiration / Q000187:drug effects; D013552:Swine
D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D010622:Phencyclidine