Tiletamine
2-(ethylamino)-2-thiophen-2-ylcyclohexan-1-one
Overview
Tiletamine belongs to Dissociatives / Arylcyclohexylamines.
Effects
- Rapid dissociative anaesthesia: analgesia and catalepsy with open eyes, detachment from the environment.
- Muscle rigidity and involuntary movements, with excessive salivation.
- A prolonged, sometimes rough or convulsive recovery with hypersensitivity to stimulation (the reason zolazepam is co-administered).
Dosing & duration
Injectable (IM/IV) veterinary anaesthetic, given by a veterinarian as the zolazepam combination (Telazol/Zoletil). There is no established or safe human dose. Figures are veterinary context only.. Tiletamine is dosed by body weight and titrated by a veterinarian as part of the zolazepam combination, with monitoring of airway, breathing and circulation. It has no validated human use. Diverted veterinary product is dangerous: the concentration and dose are formulated for animals and the dissociative effect is intense and unpredictable.
Dose ranges
Duration
Rapid (IM/IV)
≈30 min surgical anaesthesia (Telazol combination)
Prolonged, sometimes rough recovery
Chemical & Physical Properties
| Formula | C12H17NOS |
| Molar mass | 223.34 g/mol |
| State | Solid (usually the hydrochloride salt [Telazol/Zoletil], an odourless white crystalline powder, no experimental melting point reported for the free base) |
| Melting point | 186–188 °C (decomposes): hydrochloride salt (CAS 14176-50-2) |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | Not reported |
| LogP | 2 (predicted, XLogP3, free base) |
| Solubility | Hydrochloride salt is water-soluble (Telazol is reconstituted in water) |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 14176-49-9 |
| CAS (enantiomer) | |
| PubChem CID | 26533 |
| InChIKey | QAXBVGVYDCAVLV-UHFFFAOYSA-N |
| InChI | InChI=1S/C12H17NOS/c1-2-13-12(11-7-5-9-15-11)8-4-3-6-10(12)14/h5,7,9,13H,2-4,6,8H2,1H3 |
| SMILES | CCNC1(CCCCC1=O)C2=CC=CS2 |
Synonyms
- Telazol
- Zoletil
- CI-634
Pharmacodynamics & Biochemistry
Tiletamine is a dissociative anaesthetic of the arylcyclohexylamine class and a close relative of ketamine. It replaces ketamine's chlorophenyl group with a thiophene ring and its N-methyl with an N-ethyl group. Like the rest of the class it is an open-channel (non-competitive) antagonist at the NMDA glutamate receptor: it binds inside the ion channel at the phencyclidine (PCP) site and blocks it use-dependently, dissociating the cortex from sensory input to produce profound analgesia and catalepsy with the eyes open rather than classic sleep. A tiletamine-specific binding study found it displaces [³H]TCP from the NMDA-coupled PCP recognition site with an IC50 of about 79 nM (rat brain), and it is a more potent NMDA blocker than ketamine (relative potency order MK-801 > PCP > tiletamine > ketamine). It is also longer-acting than ketamine, but on its own it produces poor muscle relaxation, marked rigidity and a rough, sometimes convulsive recovery. For that reason it is almost never given alone: the marketed product Telazol (US) / Zoletil (elsewhere) combines it 1:1 with the benzodiazepine zolazepam, which smooths induction and recovery and counters the muscle rigidity and seizures, giving roughly half an hour of surgical anaesthesia. Tiletamine has a single quaternary stereocentre and is used as the racemate (the enantiomers are depicted here, but no single-enantiomer preparation is marketed). It is metabolised in the liver and excreted renally.
Biological targets
- NMDA
Binding & functional measurements
Pharmacokinetics
| Bioavailability | Not reported |
| Tmax | Not reported |
| Half-life | Species-dependent, longer-acting than ketamine |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Hepatic |
| Excretion | Renal |
Toxicology & Safety
Not reported
Tiletamine is a potent veterinary dissociative anaesthetic with a narrow, species-dependent safety margin and no role in human medicine. Used alone it causes muscle rigidity, tremor and frank convulsions and a prolonged, rough (sometimes delirious) recovery: the reason it is marketed only in combination with zolazepam. It depresses breathing and can cause apnoea and cardiovascular changes (raised heart rate and blood pressure, arrhythmias), excessive salivation, hyperthermia and increased intracranial and intraocular pressure. Recovery can be violent, with hypersensitivity to noise and touch. Human exposure is almost always through diversion of the veterinary product and is dangerous: doses are formulated for animals, the dissociation is intense and unpredictable, and, as with ketamine and PCP, aspiration and injury under anaesthesia are real risks. A recent case report described severe tremors after tiletamine e-cigarette use with alcohol. It is contraindicated in animals with significant cardiac, renal, pancreatic or CNS disease and in hyperthyroidism, and any co-use with alcohol or other CNS depressants adds respiratory-depression risk.[2]
Legal Status
US: Schedule III (Telazol combo). UK: Rx only (veterinary). DE: Prescription only (veterinary)
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- A veterinary injectable anaesthetic, used almost exclusively as the fixed combination with zolazepam (Telazol/Zoletil) for chemical restraint and surgical anaesthesia in cats, dogs and wildlife.
- Originally developed (as CI-634) in the 1960s search for ketamine-like anaesthetics. It proved too rigidity- and seizure-prone for human use.
- Occasionally misused recreationally through diversion of the veterinary product, but this is rare and hazardous.
Sources & Evidence
- PubChem: Tiletamine (CID 26533) — identifiers & computed properties
- Wikipedia: Tiletamine — arylcyclohexylamine dissociative/NMDA antagonist, Telazol/Zoletil (with zolazepam), veterinary use & legal status CC BY-SA 4.0
- Rao TS, Contreras PC, Cler JA, et al. (1991). Contrasting neurochemical interactions of tiletamine, a potent phencyclidine (PCP) receptor ligand, with the N-methyl-D-aspartate-coupled and -uncoupled PCP recognition sites. J Neurochem 56:890-7.
PMID 1847186 · doi:10.1111/j.1471-4159.1991.tb02005.x
- DEA / 21 CFR 1308.13: the tiletamine–zolazepam combination (Telazol) is a Schedule III controlled substance. Tiletamine alone is not separately scheduled