R-citalopram attenuates anxiolytic effects of escitalopram in a rat ultrasonic vocalisation model.
Escitalopram mediates the serotonin reuptake inhibitory effect of citalopram. To investigate the potential interactive effects between escitalopram and R-citalopram, they were studied at standard and elevated serotonin levels in a model predictive of anxiolytic activity (inhibition of footshock-induced ultrasonic vocalisation in adult rats). At standard levels, citalopram partially inhibited (64%) and escitalopram abolished (97%) vocalisation. Co-treatment with L-5-hydroxytryptophan resulted in complete inhibition with citalopram and a substantially enhanced response to escitalopram, while R-citalopram increased the vocalisation significantly. Furthermore, R-citalopram attenuated the effect of escitalopram. These findings may be relevant to the enhanced clinical efficacy seen with escitalopram compared to citalopram.
Sánchez
Connie
C
Neuropharmacological Research, H. Lundbeck A/S, Ottiliavej 9, DK 2500 Copenhagen-Valby, Denmark. cs@lundbeck.com
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology*; D004347:Drug Interactions; D004597:Electroshock / Q000379:methods; D005528:Foot; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013018:Sound Spectrography / Q000379:methods; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects* / Q000502:physiology
D006916:5-Hydroxytryptophan; D014151:Anti-Anxiety Agents; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors