Comparison of pharmacodynamic effects of the non-competitive NMDA receptor antagonists MK-801 and ketamine in pigs.
European Journal of Pharmacology January 17, 1991 DOI: 10.1016/0014-2999(91)90228-i (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Pigs, including a group genetically susceptible to malignant hyperthermia induced by volatile anesthetics |
| Interventions | MK-801 Ketamine Pentobarbital |
| Dose | MK-801 0.1-1.6 mg/kg; ketamine 15 mg/kg |
| Topics | Esketamine Ketamine |
| Key findings | MK-801 (0.1-1.6 mg/kg) and ketamine (15 mg/kg) produced nearly the same behavioral and physiological effects in pigs, including stereotypies, 'psychotic' behavior, and anesthetic effects, with both lowering heart rate and raising respiration rate and body temperature. MK-801 had a much longer duration of action and more pronounced catalepsy. The authors argue its resemblance to phencyclidine and ketamine makes clinical use as an anticonvulsant or anxiolytic unlikely, but suggest it may suit use as a long-acting dissociative anesthetic. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 2
- Pharmacodynamic effects of serotonin (5-HT) receptor ligands in pigs: stimulation of 5-HT2 receptors induces malignant hyperthermia. Naunyn-Schmiedeberg's Archives of Pharmacology June 1, 1990
- MK-801, a proposed noncompetitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behavioral effects in pigeons, rats and rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics June 1, 1988