Delving into the Latest Updates on BW-737C89 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

D1 receptor

Action

antagonists

Mechanism

D1 receptor antagonists(Dopamine D1 receptor antagonists)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Psychotic DisordersSchizophrenia

Originator Organization

Glaxo Group Ltd.

Active Organization-

Inactive Organization

Wellcome Laboratories

Glaxo Group Ltd.

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

The in vitro affinities (KIs) for SCH 23390 in D1, D2 and 5-HT2 binding assays were 0.4, 631 and 20 nM as compared with 0.3, 79 and 79 nM for BW737C89. The KB values, derived from their abilities to right-shift dopamine-mediated dose-dependent increases in striatal adenylyl cyclase activity, were 0.8 and 0.5 nM for SCH 23390 and BW737C89, respectively. Thus, BW737C89 was a highly potent dopamine D1 receptor antagonist and, although it was less D1/D2-selective than SCH 23390, it was more D1/5-HT2-selective. Both SCH 23390 and BW737C89 (0.1-100 mumol/kg s.c.) exhibited a selective dose-dependent protection of D1, but not D2, binding, from inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 8 mg/kg s.c.) as measured by [3H]SCH 23390 (D1) and [3H]spiperone (D2) binding. The ED50 values for this selective protection of D1 binding were similar and were between 1 and 3 mumol/kg s.c. BW737C89 showed no protective effect at all on the inactivation of [3H]ketanserin (5-HT2) binding by EEDQ whereas SCH 23390 started to show protection at doses of 10 mumol/kg s.c. and above. A direct comparison of the time course of the effects of pretreatment of a dose of 30 mumol/kg s.c. of both compounds to protect 5-HT2 binding was carried out. This study confirmed the complete lack of protective effect of BW737C89 from 1 to 4 h of pretreatment whereas SCH 23390 exhibited 62, 29 and 28% protection at 1, 2 and 4 h pretreatment respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

100 Deals associated with BW-737C89

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