Lypressin

Summary

Lypressin (8‑lysine vasopressin) is a synthetic nonapeptide analogue of vasopressin that was marketed as a prescription drug but has since been withdrawn. It has been investigated for its antidiuretic action in diabetes insipidus and for raising blood pressure in chronic orthostatic hypotension.

Mechanism of Action

Lypressin binds to the same vasopressin receptors as the natural hormone. Activation of V1 receptors on vascular smooth muscle produces vasoconstriction, increasing systemic vascular resistance and blood pressure. Activation of V2 receptors in the renal collecting ducts promotes water reabsorption, reducing urine output. The lysine substitution prolongs its activity compared with native vasopressin.

What the Research Shows

Evidence for lypressin is limited. A 1985 small clinical study in ten patients with chronic orthostatic hypotension showed that nasal administration (two sprays, 7.4 µg total) raised blood pressure and total peripheral resistance without significantly altering heart rate, stroke volume, or cardiac output. A 2022 review of vasopressin analogues notes that lypressin has been used to treat diabetes insipidus, leveraging its antidiuretic V2 activity. No large‑scale trials, systematic safety evaluations, or recent efficacy data are available, and the product has been withdrawn from the market.

Reported Benefits

When used, lypressin can provide antidiuretic effects useful in managing central diabetes insipidus, reducing polyuria and polydipsia. In the orthostatic hypotension study, it modestly increased systolic blood pressure and peripheral resistance, suggesting potential benefit for patients with refractory postural drops in pressure.

Limitations of the Evidence

Clinical data are sparse and derived from small, uncontrolled studies. The drug is no longer marketed, and regulatory status is withdrawn, indicating unresolved safety or efficacy concerns. No comparative trials versus other vasopressin analogues (e.g., desmopressin) have been reported, and its role in modern practice remains undefined.

Safety Considerations

In the orthostatic hypotension trial, lypressin did not cause marked tachycardia or cardiac output decline, but vasoconstriction can exacerbate underlying cardiac or pulmonary disease. As with other vasopressin analogues, risks include hyponatremia, ischemic events, and reduced renal perfusion. The withdrawn status reflects insufficient safety data for continued use.

How It Is Administered

Lypressin has been formulated for intravenous injection, subcutaneous injection, and intranasal spray. Dosing regimens reported in the literature involve low‑dose nasal sprays (approximately 7 µg per administration) or intravenous bolus doses comparable to other vasopressin preparations. Specific dosing recommendations are not provided in current sources.

Routes of Administration

Goals & Uses

• Control of bleeding from esophageal varicesGastrointestinalModerate
• Treatment of central diabetes insipidusEndocrine / RenalModerate
• Management of central diabetes insipidusEndocrinologyModerate
• Reduction of polydipsiaSymptomatic ReliefModerate
• Reduction of polyuriaSymptomatic ReliefModerate

Contraindications

• Severe hyponatremiaElectrolyteHigh
• Known hypersensitivity to vasopressin analogsAllergyHigh
• Hypersensitivity to vasopressin or analoguesImmunologicHigh
• HypertensionCardiovascularModerate
• PregnancyPopulationModeratePotential fetal risk or insufficient safety data
• Unstable cardiovascular disease (e.g., recent MI)CardiovascularModerate
• Coronary artery diseaseCardiovascularHigh
• Nephrogenic diabetes insipidusRenalHigh

Adverse Effects

• Nasal congestion and rhinitisLocal / NasalCommon
• Hyponatremia / water intoxicationMetabolicRare
• HeadacheNeurologicCommonPain in the head or upper neck
• Myocardial ischemiaCardiovascularRare
• Abdominal crampsGastrointestinalUncommon
• Pallor and vasoconstrictionCardiovascularUncommon
• HyponatremiaElectrolyteCommon
• Angina pectorisCardiovascularRare

Drug Interactions

• Loop diureticsModerate
• Tricyclic antidepressantsLow
• NSAIDsLowMay increase renal risk in susceptible patients
• ChlorpropamideModerate
• Thiazide diureticsHigh
• LithiumModerate
• Vasodilators (e.g., nitroglycerin)Low

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patientsAgeRelative
• ElderlyAgeRelative
• Elderly patientsAgeRelative
• Pregnant womenReproductiveRelative
• Patients with chronic renal diseaseRenal ImpairmentRelative

Regulatory Status

• European UnionApprovedApproved: central diabetes insipidus, esophageal variceal bleedingApproved in several EU member states under local brand names.
• JPApprovedApproved: central diabetes insipidusMarketed as Lypressin in Japan.
• United StatesUnapprovedNot FDA‑approved; considered investigational.
• United KingdomUnknownNot currently listed as an approved product in the UK; desmopressin is preferred.

Approved for medical use in several non‑US jurisdictions (e.g., Japan, some European countries). Not FDA‑approved in the United States; considered investigational there.

Evidence & Sources

• Terlipressin: vasopressin analog and novel drug for septic shock
  Journal ArticleModeratePesaturo AB, Jennings HR, Voils SA2006-01-01T00:00:00.000000Z
• Quantitative analysis of nonapeptides in pharmaceutical dosage forms by high-performance liquid chromatography
  Journal ArticleLowKrummen K, Frei RW1977-01-01T00:00:00.000000Z
• Hemodynamic effects of lysine-vasopressin in orthostatic hypotension
  Journal ArticleLowKochar MS1985-01-01T00:00:00.000000Z
• Vasopressin and Its Analogues: From Natural Hormones to Multitasking Peptides
  Journal ArticleModerateGlavaš M, et al.2022-01-01T00:00:00.000000Z
• Safety and tolerability of treatments for allergic rhinitis in children
  Journal ArticleModerateBaena-Cagnani CE2004-01-01T00:00:00.000000Z
• Hepatorenal Syndrome
  Journal ArticleModerateFrancoz C, et al.2019-01-01T00:00:00.000000Z

Frequently Asked Questions