Abstract:
:The aim of this work is to investigate the therapeutic efficacy of VP-343 ((N-[4-[[(2S,3aR)-2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-a]qunoxalin-5(1H)-yl]phenyl]-4'-methyl[1,1'-biphenyl]-2-carboxamide), a selective vasopressin V2 receptor antagonist, using the experimental SIADH (syndrome of inappropriate secretion of antidiuretic hormone) rat model. In the model, which was accomplished by administering continuously 1-desamino-8-D-arginine vasopressin (DDAVP), serum sodium levels (S(Na)) and serum osmolarity levels (S(Osm)) significantly and remarkably decreased, which was accompanied with hyper-osmolarity of urine and oliguria. VP-343 increased rapidly and dose-dependently S(Na) and S(Osm). VP-343 exhibited marked diuretic action and decreased urine osmolarity dose-dependently. In the SIADH rat model, all serum levels of chloride, calcium, creatinine, total cholesterol, and uric acid decreased when compared with normal levels. VP-343 increased all serum levels of chloride, calcium, and total cholesterol. These results indicate that VP-343 has efficacy to normalize the abnormalities in DDAVP-induced SIADH.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Naito A,Hasegawa H,Kurasawa T,Ohtake Y,Matsukawa H,Ezure Y,Tsuriya Y,Koike K,Shigenobu Kdoi
10.1248/bpb.23.1323subject
Has Abstractpub_date
2000-11-01 00:00:00pages
1323-7issue
11eissn
0918-6158issn
1347-5215journal_volume
23pub_type
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