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