VASOPRESSIN RECEPTOR ANTAGONISTS AND IT’S THERAPEUTIC POTENTIAL

Dr Amit mittalTutorDepartment of PharmacologyLLRM Medical College,Meerut

Vasopressin(Antidiuretic hormone)A nonapeptide hormoneMammalian ADH-8 Arginine

vasopressin(AVP)Synthesized in hypothalamus and

transported to the posterior pituitary where it is stored

ACTIONS OF ADH- KIDNEY-act on CD and increase water

permeability BLOOD VESSEL-cause vasoconstriction CNS-regulation of

temperature,ACTHrelease,tasks learning Visceral smooth muscle contraction Increased peristalsis in gut Induce platelet aggregation Cause hepatic glycogenolysis Release coagulation factor Vlll and von

Willebrands’factor from vascular endothelium

Stimuli for ADH secretion Hypovolaemia Hyperosmolarity Pain,Stress,Anxiety,Nausea Drugs

Acetylcholine Nicotine Morphine Indomethacin Histamine Prostaglandins Chlorpropamide Carbamazepine General Anaesthetics

Some chronic conditionsCHFCirrhosisProlonged use of diuretics

Inhibition of ADH Ethanol Phenytoin Glucocorticoids GABA ANP

• REGULATION OF OSMOLARITY OF EXTRACELLULAR FLUID

Vasopressin ReceptorsG Protein Coupled Cell

Membrane ReceptorThree types

V1a V1b(V3) V2

VASOPRESSIN RECEPTOR ANTAGONIST- Peptide group Non-Peptide group

CONIVAPTAN TOLVAPTAN LIXIVAPTAN RELCOVAPTAN SSR-149414 SATAVAPTAN MOZAVAPTAN

CONIVAPTAN- Non selective (V2+V1a) IV formulation only Euvolaemic and Hypervolaemic Hyponatraemia Acute heart failure with hyponatraemia Cirrhosis with ascites Nephrotic syndrome

TOLVAPTAN- V2 selective Oral Used in hyponatraemia due to Congestive heart

failure,Cirrhosis,SIADH Dose-15-45mg/day

LIXIVAPTAN- V2 selective Oral

DRUGS UNDER CLINICAL TRIAL

RELCOVAPTAN- V1a selective Raynaud’s disease Dysmenorrhea Tocolytic

SSR-149415- V1b selective Psychiatric disorder

SATAVAPTAN (V2 selective)MOZAVAPTAN

S/E- Dry mouth Constipation Polyuria Polydipsia Fever Postural hypotension Weakness