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The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.
- Source :
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Psychopharmacology . Sep2021, Vol. 238 Issue 9, p2393-2403. 11p. 2 Diagrams, 2 Charts, 1 Graph. - Publication Year :
- 2021
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Abstract
- Rationale: Arginine vasopressin (AVP) is a neuropeptide that modulates both physiological and emotional responses to threat. Until recently, drugs that target vasopressin receptors (V1a) in the human central nervous system were unavailable. The development of a novel V1a receptor antagonist, SRX246, permits the experimental validation of vasopressin's role in the regulation of anxiety and fear in humans. Objectives: Here, we examined the effects of SRX246 in a proof-of-concept translational paradigm of fear (phasic response to imminent threat) and anxiety (prolonged response to potential threat). Methods: Healthy volunteers received both SRX246 and placebo in a randomized, double-blind, counter-balanced order separated by a 5–7-day wash-out period. Threat consisted of unpleasant electric shocks. The "NPU" threat test probed startle reactivity during predictable threat (i.e., fear-potentiated startle) and unpredictable threat (i.e., anxiety-potentiated startle). Results: As predicted, SRX246 decreased anxiety-potentiated startle independent of fear-potentiated startle. Conclusions: As anxiety-potentiated startle is elevated in anxiety and trauma-associated disorders and decreased by traditional anxiolytics such as SSRIs and benzodiazepines, the V1a receptor is a promising novel treatment target. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00333158
- Volume :
- 238
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 151976419
- Full Text :
- https://doi.org/10.1007/s00213-021-05861-4