Dataset Information

The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.

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.

SUBMITTER: Lago TR

PROVIDER: S-EPMC8376758 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.

Lago Tiffany R TR Brownstein Michael J MJ Page Emily E Beydler Emily E Manbeck Adrienne A Beale Alexis A Roberts Camille C Balderston Nicholas N Damiano Eve E Pineles Suzanne L SL Simon Neal N Ernst Monique M Grillon Christian C

Psychopharmacology 20210510 9

<h4>Rationale</h4>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.<h4>Objectives</h4>Here, we examined the effects of SRX246 in a proof-of-concept trans ...[more]

PMID: 33970290

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Dataset Information

The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.

Rationale

Objectives

Methods

Results

Conclusions

Publications

The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.

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