Lysopressin

Lysopressin (lypressin) is a synthetic analog of porcine antidiuretic hormone, differing from human arginine vasopressin by a single amino acid substitution (lysine instead of arginine at position 8). It was historically used as a nasal spray formulation (marketed as Diapid by Sandoz) for treating vasopressin-deficient diabetes insipidus from the 1960s through the 1980s. While effective at controlling polyuria through V2 receptor-mediated water reabsorption in the renal collecting ducts, lysopressin has been largely replaced by desmopressin (DDAVP) due to its shorter duration of action (3-4 hours) and requirement for more frequent dosing. Lysopressin is also the active metabolite of terlipressin, a prodrug used in managing hepatorenal syndrome and variceal bleeding in liver cirrhosis.

Antidiuretic Effects for Diabetes Insipidus

Lysopressin was proven effective in managing central diabetes insipidus, with clinical studies demonstrating successful control of polyuria in patients who were treated with nasal spray formulations administered 2-8 times daily ^[1][2][3]. The synthetic preparation offered several advantages over earlier animal-derived vasopressin products, including ease of administration, minimal risk of water retention when used appropriately, and freedom from potentially serious allergic reactions to foreign proteins ^[4]. In patients who experienced local or systemic reactions to other exogenous forms of vasopressin, lysopressin nasal spray provided satisfactory disease control ^[4][5].

Mechanism of Action

Lysopressin acts primarily through V2 receptors located on the basolateral membrane of principal cells in the renal collecting duct, activating adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) levels ^[6][7]. This signaling cascade leads to increased transcription and insertion of aquaporin-2 water channels into the apical membrane of collecting tubule epithelial cells, facilitating water reabsorption and enabling excretion of more concentrated urine ^[8]. The peptide also exhibits V1 receptor activity, mediating vasoconstriction and other peripheral effects through phospholipase C–IP3/DAG pathway activation ^[9].

Cardiovascular and Hemostatic Effects

Beyond its antidiuretic properties, lysopressin demonstrates cardiovascular effects that vary by route of administration. Intravenous administration produces dose-dependent increases in blood pressure and decreases in heart rate, while intracisternal administration produces opposite effects, likely through decreased sympathetic tone ^[10]. In patients with liver cirrhosis, lysopressin infusion increases factor VIII, factor VIII-related antigen, and plasminogen activator levels, contributing to hemostatic effects ^[11]. As the active metabolite of terlipressin, lysopressin plays a crucial role in managing portal hypertensive bleeding and hepatorenal syndrome through splanchnic vasoconstriction and improved renal perfusion ^[12].

Historical Clinical Utility

Historical clinical trials from the 1960s-1970s established lysopressin as a valuable therapeutic option for patients with vasopressin-deficient diabetes insipidus, particularly those intolerant to other vasopressin preparations ^[4][5]. The medication was particularly useful for partial central diabetes insipidus due to its lower cost compared to newer alternatives, though it required more frequent administration ^[13].

Common Side Effects and Administration

Lysopressin nasal spray was generally well-tolerated in clinical studies, with most patients experiencing successful disease control without recurrence of side effects occasionally observed with posterior pituitary preparations of animal origin ^[1][2]. The formulation required frequent administration (3-5 times daily) due to its relatively short duration of action, with antidiuretic effects lasting only 3-4 hours compared to the longer-acting desmopressin ^[13]. Patients successfully treated with lysopressin typically required applications every three hours during the day but none during the night ^[3].

Cardiovascular and Vasopressor Effects

As a vasopressin analog, lysopressin exhibits vasopressor activity through V1 receptor activation, which can cause peripheral vasoconstriction and blood pressure elevation ^[9][10]. Intravenous administration produces dose-dependent increases in blood pressure and decreases in heart rate ^[10]. These pressor effects are less selective than those of desmopressin, which demonstrates preferential V2 receptor activity and markedly diminished pressor activity ^[13]. The cardiovascular effects necessitate caution in patients with hypertension or cardiovascular disease.

Metabolic and Endocrine Considerations

Excessive use or inappropriate dosing of lysopressin can lead to water retention and hyponatremia, though these effects are generally avoidable with judicious administration ^[4]. Pediatric and geriatric populations are thought to be more sensitive to the effects of vasopressin analogs and may require dose adjustments . Clinical signs following overdose are expected to be exaggerations of known physiologic responses to the hormone, including hypertension from peripheral vasoconstriction and excessive antidiuresis .

Discontinuation and Current Status

Lysopressin-containing nasal spray (marketed as Diapid by Sandoz/Novartis) has been discontinued from commercial marketing . The medication has been largely replaced by desmopressin (DDAVP), which offers superior pharmacokinetic properties including longer duration of action (requiring less frequent administration), enhanced antidiuretic potency, fewer pressor effects due to V2-selective actions, and a prolonged half-life ^[13]. Lysopressin demonstrated a plasma half-life of 2.5 and 14.5 minutes for fast and slow phases respectively, compared to 7.8 and 75.5 minutes for desmopressin ^[13]. While lysopressin may remain available on a compassionate-use basis from the manufacturer, it is no longer a standard treatment option for diabetes insipidus .

Contraindications and Precautions

Patients with known hypersensitivity to lysopressin or other vasopressin analogs should avoid use ^[4][5]. Due to its vasoconstrictive properties, caution is warranted in patients with coronary artery disease, peripheral vascular disease, or conditions that may be exacerbated by fluid retention. The medication should be used carefully to avoid water intoxication and electrolyte imbalances, with monitoring of urine output, body weight, and serum sodium levels recommended during treatment ^[4].