Vasopressin

A cyclic nonapeptide hormone, also called antidiuretic hormone, that controls renal water reabsorption and vascular tone through V1a, V1b, and V2 receptors and is FDA approved as an intravenous vasopressor.

Also referenced as: AVP, Arginine Vasopressin, Antidiuretic Hormone, ADH, Argipressin, Vasostrict, Pitressin

Also appears in: Cardiovascular

What is vasopressin?

Vasopressin is a cyclic nonapeptide (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2) closed by a disulfide bridge between Cys1 and Cys6, synthesized in magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei and released from the posterior pituitary. It is the body’s antidiuretic hormone (ADH), and it differs from oxytocin at only two positions — phenylalanine for isoleucine at residue 3, and arginine for leucine at residue 8 — which is why the two peptides share a scaffold but not a physiology.

It reaches the research-compound market for two unrelated reasons: it is a long-standing laboratory reference peptide with an approved hospital drug product behind it, and the V1a receptor literature on pair bonding, social recognition, and memory has kept it adjacent to the oxytocin conversation that drives most consumer interest in neurohypophyseal peptides.

How it works

Vasopressin signals through three G-protein-coupled receptor subtypes, and the tissue distribution of those subtypes is the source of its pharmacological breadth:

• V2 receptors (kidney) — Gs-coupled signaling in collecting duct principal cells raises cAMP and drives aquaporin-2 water channels into the apical membrane, increasing water reabsorption and concentrating urine (Nielsen et al., Physiological Reviews, 2002, 82(1):205–244)
• V1a receptors (vascular smooth muscle) — Gq-coupled signaling raises intracellular calcium and produces vasoconstriction; vasopressin retains pressor activity in states where catecholamine receptors are desensitized, which is the rationale for its critical-care use (Holmes et al., Critical Care, 2003, 7(6):427–434)
• V1b receptors (anterior pituitary corticotrophs) — potentiate CRH-driven ACTH release, placing vasopressin inside the HPA stress axis rather than only the fluid-balance system (Antoni, Frontiers in Neuroendocrinology, 1993, 14(2):76–122)
• Central V1a receptors (social behavior) — V1a signaling in the forebrain is required for partner preference in monogamous prairie voles, and transgenic expression of the vole V1a receptor increases affiliative responses to vasopressin in mice (Winslow et al., Nature, 1993, 365(6446):545–548; Young et al., Nature, 1999, 400(6746):766–768)

Vasopressin also binds the closely related oxytocin receptor, which is a persistent confound in the behavioral literature rather than a separate therapeutic axis.

Research status

Vasopressin has a genuine FDA approval and a large, mixed clinical literature — including several prominent negative trials.

Approved use. Vasostrict (NDA 204485) was approved April 17, 2014 under the FDA pathway for drugs already marketed without an approved NDA, indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. Multiple generic and 505(b)(2) vasopressin injections have since been approved.

Critical care.

• VASST — Russell et al. (2008) found no significant 28-day mortality reduction with low-dose vasopressin versus norepinephrine in septic shock (35.4% vs 39.3%; P = 0.26); a survival signal appeared only in a prespecified less-severe-shock stratum (26.5% vs 35.7%; P = 0.05) (New England Journal of Medicine, 358(9):877–887)
• VANISH — Gordon et al. (2016) found no increase in kidney failure–free days with early vasopressin versus norepinephrine, though fewer vasopressin patients received renal replacement therapy (25.4% vs 35.3%) (JAMA, 316(5):509–518)
• VANCS — Hajjar et al. (2017) reported a lower composite rate of mortality and severe complications with vasopressin versus norepinephrine in vasoplegic shock after cardiac surgery (32% vs 49%; HR 0.55) (Anesthesiology, 126(1):85–93)
• Cardiac arrest — Wenzel et al. (2004) compared vasopressin with epinephrine in out-of-hospital resuscitation without an overall survival advantage (New England Journal of Medicine, 350(2):105–113); the American Heart Association removed vasopressin from the adult cardiac arrest algorithm in its 2015 ACLS guideline update

Social behavior and memory. de Wied (1971) reported that vasopressin preserved a conditioned avoidance response in rats (Nature, 232:58–60), launching a “vasopressin-memory hypothesis” that was challenged within a decade (Sahgal, Psychopharmacology, 1984, 83:215–228) and is now generally treated as unsupported; Leng et al. traced the rise and collapse of that debate through citation-network analysis (Annals of the New York Academy of Sciences, 2019). In humans, Thompson et al. (2006) found sex-divergent effects of intranasal vasopressin on responses to unfamiliar faces (PNAS, 103(20):7889–7894). Parker et al. (2019) ran a four-week randomized placebo-controlled pilot of intranasal vasopressin in 30 children with autism and reported improved social responsiveness scores (Science Translational Medicine, 11(491):eaau7356). The larger Stanford follow-up (NCT03204786, Phase 2/3, 108 randomized of 157 consented) completed in March 2024 and posted results to ClinicalTrials.gov in September 2025; no peer-reviewed report of that trial has appeared to date.

The opposite pharmacology also failed. Balovaptan, a V1a antagonist, was stopped for futility in the Phase 3 V1aduct trial and showed no advantage over placebo on socialization and communication in autistic adults (Jacob et al., Lancet Psychiatry, 2022, 9(3):199–210) — a reminder that the V1a–social-behavior link has not translated in either direction. On the delivery question, Talbot et al. (2024) showed nebulized vasopressin reaching cerebrospinal fluid in rhesus macaques (PNAS, 121(49):e2418635121).

Common dosage forms

• Approved pharmaceutical — sterile aqueous injection at 20 units/mL in single-dose and multiple-dose vials requiring dilution, plus ready-to-use premixed single-dose vials of vasopressin in 5% dextrose at 0.2, 0.4, 0.6, and 1 unit/mL. Intravenous administration only. Strength is expressed in units, not milligrams, which does not translate to milligram-based peptide labeling.
• Research supply — lyophilized arginine vasopressin acetate powder in milligram quantities, typically sold as an analytical reference peptide or receptor-assay reagent rather than as a consumer research compound.
• Intranasal — the nasal formulations used in autism research are investigational or compounded. There is no marketed intranasal vasopressin product in the United States; the outpatient antidiuretic role is filled by desmopressin, which is available as tablets, nasal spray, and injection.

Key considerations

• The approval is narrow. Vasopressin is approved only as an intravenous vasopressor for vasodilatory shock in adults. Nothing about that approval extends to social, cognitive, anti-aging, or wellness framing. Before 2014 it was sold in the U.S. as an unapproved marketed drug (Pitressin), so older product literature describes formulations the FDA never reviewed.
• Label safety signals are dose-related and specific. The approved labeling lists coronary, mesenteric, skin, and digital ischemia; hyponatremia; decreased cardiac output; bradycardia and tachyarrhythmias; and reversible diabetes insipidus with polyuria and hypernatremia after discontinuation.
• Central delivery remains the core evidence gap. Peripherally administered vasopressin crosses into cerebrospinal fluid poorly, and whether intranasal dosing reaches central V1a receptors at behaviorally relevant concentrations in humans is still unsettled — the single strongest reason the behavioral literature has not converged.
• Oxytocin cross-reactivity is a real confound. Because vasopressin and oxytocin differ by two residues, each binds the other’s receptors with meaningful affinity, so behavioral effects attributed to one peptide are difficult to isolate (Song & Albers, Frontiers in Neuroendocrinology, 2018, 51:14–24).
• Naming is genuinely confusing. Vasopressin (AVP/ADH) is not desmopressin (DDAVP, a V2-selective analog), terlipressin (Terlivaz, approved in September 2022 for hepatorenal syndrome), or lypressin (lysine vasopressin, used in much of the older behavioral work). Endocrine societies also renamed central and nephrogenic diabetes insipidus to AVP deficiency (AVP-D) and AVP resistance (AVP-R) in 2022 (Arima et al., Journal of Clinical Endocrinology & Metabolism, 2022, 108(1):1–3).