Tolvaptan is a selective and competitive arginine vasopressin receptor 2 antagonist. Vasopressin acts on the V2 receptors found in the walls of the vasculature and luminal membranes of renal collecting ducts. By blocking V2 receptors in the renal collecting ducts, aquaporins do not insert themselves into the walls thus preventing water absorption. This action ultimately results in an increase in urine volume, decrease urine osmolality, and increase electrolyte-free water clearance to reduce intravascular volume and an increase serum sodium levels. Tolvaptan is especially useful for heart failure patients as they have higher serum levels of vasopressin. Tolvaptan is used to treat low blood sodium levels (hyponatremia) associated with various conditions like congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormones (SIADH). FDA approved on May 19, 2009. Tolvaptan is sold under the trade names Samsca and Jinarc.

Conivaptan is an arginine vasopressin (AVP) receptor antagonist with affinity for AVP receptor subtypes V1A and V2. The antidiuretic action of AVP is mediated through activation of the V2 receptor, which functions to regulate water and electrolyte balance at the level of the collecting ducts in the kidney. Conivaptan was approved in 2004 for hyponatremia caused by syndrome of inappropriate antidiuretic hormone. Conicaptan is being evaluated for reduce intracranial pressure in patients with traumatic brain injury, and as a treatment for heart failure.

Relcovaptan is a potent, orally active nonpeptide vasopressin V1a antagonist that was undergoing clinical development with Sanofi-Synthélabo (formerly Sanofi) in France. SR49059 is specifically and selectively antagonizes the effect of vasopressin on the V1a receptor in animals’ and in humans. The drug has been shown to have an excellent safety profile in single and repeated dose toxicological studies in animals. In the human uterus in vitro, SR49059 caused a dose-dependent inhibition of vasopressin V1a receptor-mediated activity of myometrial strips and isolated uterine arteries. In vivo in nonpregnant women, an inhibition of vasopressin-induced uterine activity has been observed.

Lixivaptan is an orally-active, vasopressin 2 receptor antagonist. It is indicated for the treatment of symptomatic hypervolemic and euvolemic hyponatremia, associated with heart failure (HF) and syndrome of inappropriate antidiuretic hormone (SIADH). Adverse events likely to be result of the pharmacologic action of lixivaptan are: constipation, dry mouth, dizziness, insomnia. Grapefruit juice significantly increased the extent of lixivaptan absorption as compared to lixivaptan administered under fasted conditions but not under fed conditions. Lixivaptan Cmax and AUC∞ increased by 2.4-fold and 3.2-fold, respectively, when lixivaptan was administered with ketoconazole (the same in case of Simvastatin).

Fedovapagon, also known as VA106483 and VT483, is a potent, nonpeptidic vasopressin V2 receptor agonist. Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. Fedovapagon (VA106483) was discovered by Vantia and currently in Phase II trials for the treatment of nocturia, a common condition that causes sufferers to wake frequently during the night in order to urinate. Fedovapagon has been extensively studied in clinical trials and data, presented at the American Urological Association meeting in 2010, demonstrated a dose-dependent reduction in nocturnal urine volumes and a reliable pharmacodynamic effect on repeated dosing. More recently, data presented in San Diego at the 2012 American Urological Association meeting, showed that fedovapagon was effective from the first night of dosing and that there was no effect following cessation of dosing. Further presentations are planned for the International Continence Society meeting being held in Barcelona in August 2013. These data suggest that fedovapagon has the potential to be an effective and well tolerated antidiuretic for the treatment of nocturia. Fedovapagon is currently being investigated as a new treatment for nocturia in a Phase-II/III clinical trials in USA (PO)(NCT02637960).

TC OT 39 was developed as potent non-peptide oxytocin receptor partial agonist and V2 vasopressin receptor agonist. Also was a V1a vasopressin receptor antagonist.

Ornipressin (ornithine-8-vasopressin, POR-8), is a synthetic vasopressin analogue. Ornipressin produces vasoconstriction via vasopressin V1A receptor-mediated vascular smooth muscle cell contraction. Ornipressin is used to control bleeding in surgical practice. It was introduced in 1971, and approved for use in Germany, Switzerland, New Zealand and Australia.

Mozavaptan hydrochloride was approved by Pharmaceuticals and Medical Devices Agency of Japan (PMDA) on July 26, 2006. It was developed and marketed as Physuline® by Otsuka in Japan. Mozavaptan hydrochloride is a vasopressin receptor antagonist. It is indicated for the treatment of hyponatremia due to excessive fluid retention when restriction of fluid intake is ineffective. Physuline® is available as film-coated tablet for oral use, containing 30 mg of Mozavaptan hydrochloride. The recommended dose is one tablet (30 mg) once daily after a meal.

Terlipressin (Glypressin) is indicated for the treatment of bleeding oesophageal varices and in some countries for the treatment of hepatorenal syndrome type 1. It is a prodrug and is converted to the lysine vasopressin in the circulation after the N-triglycyl residue is cleaved by endothelial peptidases. This results in a ‘slow release’ of the vasoactive lysine vasopressin. Terlipressin exerts its action by activating V1a, V1b and V2 vasopressin receptors. On September 14, 2022, the FDA granted approval to terlipressin (Terlivaz) for the treatment of adults hospitalized with hepatorenal syndrome with rapid reduction in kidney function (HRS-1). Prior to the approval, no approved treatment for this condition existed in the United States.