Spadin as a new antidepressant- Absence of TREK-1-related side effects-

Authors
H. Moha ou Maati, J. Veyssiere, F. Labbal, T. Coppola, C. Gandin et al.


Lab
Université de Nice Sophia Antipolis, Centre National de la Recherche Scientifique (CNRS, UMR6097), Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.

Journal
Neuropharmacology

Abstract
Despite several decades of research, current antidepressant (AD) treatments remain of a limited efficacy justifying the need to find new drugs. These drugs have to be more efficacious, more rapid and display lesser side effects. Using rodent models, we recently identified spadin as a new antidepressant molecule that acts more quickly than classical ADs, working within 4 days to get same effects obtained with other ADs after 21 days. Spadin blocks TREK-1 K(2P) potassium channels that are considered as new targets for ADs. Deletion of the TREK-1 channel is known to increase sensitivity to pain, seizures and ischemia. Thus blocking these channels could result in deleterious side effects. In this study we showed that spadin did not interfere with other TREK-1 controlled functions such as pain, epilepsy and ischemia. We also demonstrated that spadin was unable to inhibit currents generated by TREK-2, TRAAK, TASK and TRESK four other K2P channels. More importantly, spadin did not induce cardiac dysfunctions, did not block I(Kr) and I(Ks) and did not modify the systolic pressure or cardiac pulses. After a three week treatment spadin remained an efficacious AD and did not modify the infarct size in brain following focal ischemia. Finally, we showed that kainate induced seizures and glycemia were not modified by spadin treatments. These data, together with those previously published reinforce the idea that spadin represents a good candidate for a new generation of ADs. This article is part of a Special Issue entitled 'Anxiety and Depression'.

BIOSEB Instruments Used:
Forced Swimming Test: New FST DUAL SENSOR (BIO-FST-DSM)

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