Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents
Piotr Popik, Małgorzata Hołuj, Tomasz Kos, Gabriel Nowak, Tadeusz Librowski, Kinga Sałat
Neurotoxicity Research June 2, 2017 DOI: 10.1007/s12640-017-9759-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice and rats |
| Interventions | Ketamine Tiletamine |
| Dose | 10 mg/kg, 15 mg/kg, 5-15 mg/kg |
| Measures | forced swim test, marble-burying behavior, passive avoidance test, novel object recognition test, ultrasonic vocalizations (USVs), four-plate test, hot plate test, rotarod test |
| Topics | Esketamine Ketamine |
| Citations | 38 |
| Key points | Ketamine and tiletamine showed similar antidepressant-like effects and adverse-effect profiles in rodents, with tiletamine also producing anxiolytic-like effects. The authors suggest tiletamine could be an alternative to ketamine as an antidepressant with an additional anxiolytic-like profile. |
Abstract
The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine (KET) produces rapid and sustained antidepressant effects in patients. Tiletamine (TIL; 2-ethylamino-2-thiophen-2-yl-cyclohexan-1-one) is another uncompetitive NMDA receptor antagonist, used in a medical (veterinary) setting as an anesthetic tranquilizer. Here, we compared the behavioral actions of KET and TIL in a variety of tests, focusing on antidepressant-like and dissociative-like effects in mice and rats. The minimum effective doses of KET and TIL were 10 mg/kg to reduce mouse forced swim test immobility and 15 mg/kg to reduce marble-burying behavior. However, at similar doses, both compounds diminished locomotor activity and disturbed learning processes in the mouse passive avoidance test and the rat novel object recognition test. KET and TIL also reduced social behavior and accompanying 50-kHz "happy" ultrasonic vocalizations (USVs) in rats. TIL (5-15 mg/kg) displayed additional anxiolytic-like effects in the four-plate test. Neither KET nor TIL affected pain response in the hot plate test. Examination of the "side effects" revealed that only at the highest doses investigated did both compounds produce motor deficits in the rotarod test in mice. While KET produced behavioral effects at doses comparable between species, in the rats, TIL was ~10 times more potent than in the mice. In summary, antidepressant-like properties of both KET and TIL are similar, as are their adverse effect liabilities. We suggest that TIL could be an alternative to KET as an antidepressant with an additional anxiolytic-like profile.
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
Cited by 13
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
- Partial mGlu5 receptor NAM, M-5MPEP, induces rapid and sustained antidepressant-like effects in the BDNF-dependent mechanism and enhances (R)-ketamine action in mice. Pharmacological Reports June 1, 2024
- The Behavioral and Neuroinflammatory Impact of Ketamine in a Murine Model of Depression and Liver Damage. International Journal of Molecular Sciences April 10, 2025
- L-type voltage-dependent calcium channels in the ventromedial orbitofrontal and prefrontal cortices mediate the inhibitory effects of (S)-ketamine but not (R)-ketamine on marble burying in male mice European Journal of Pharmacology October 25, 2025
- Serotonergic psychedelics and amphetamine shift male rat ultrasonic vocalizations toward call patterns associated with positively valenced states. Progress in Neuro-Psychopharmacology and Biological Psychiatry September 18, 2026
and 8 more in the library
Cites 16
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Study of a New Schizophrenomimetic Drug—Sernyl Archives of Neurology And Psychiatry March 1, 1959
and 11 more in the library