Abstract

Introduction. There have been increasing reports of severe bladder toxicity, characterized by ulcerative cystitis, relating to the chronic use of ketamine. Methoxetamine, an N-ethyl derivative of ketamine, is being marketed as a “bladder safe” alternative to ketamine, however pharmacological studies have not been conducted to confirm whether or not this is the case. It has been suggested that methoxetamine is both an NMDA receptor blocker and a dopamine reuptake inhibitor. We thus tested the effects of methoxetamine in the rat nucleus accumbens to determine if it increased dopamine levels, giving us some idea of its abuse potential.
Methods. Bladder Methods: Longitudinally oriented rat urinary bladder strips from male Wistar rats (Charles River, UK, 300-500g) were suspended in organ baths containing oxygenated Krebs solution at 37°C. Tension changes were recorded using an isometric transducer. We tested methoxetamine in concentration range 10-6 to 3x10-4M. Nucleus accumbens dopamine measures: Male Wistar rat (8 weeks) were killed by cervical dislocation and 400 µm accumbens brain slices taken. Slices were superfused with oxygenated aCSF at 32.5°C. Dopamine was electrically evoked (10 pulses at 100 Hz) and measured using fast cyclic voltammetry.
Results. Methoxetamine showed a concentration dependent effect on evoked dopamine efflux, increasing peak dopamine efflux and slowing dopamine reuptake at 30 and 100 µM. 3 and 10 µM had little effect on either parameter. Bladder analysis is ongoing and results will be presented.
Conclusions. Methoxetamine, at high concentrations, is a dopamine transporter blocker and this property might be involved in its addictive liability.
Original languageEnglish
Title of host publicationRes Advanced Psychiatry
Volume1:30
Publication statusPublished - 2014
Event3rd International Conference on Novel Psychoactive Substances (NPS) - Domus Pacis, Terra Rossa, Rome, Italy
Duration: 15 May 201416 May 2014

Conference

Conference3rd International Conference on Novel Psychoactive Substances (NPS)
Country/TerritoryItaly
CityRome
Period15/05/1416/05/14

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