Delving into the Latest Updates on MDL-105212A with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

NK1R x NK2R

Mechanism

NK1R antagonists(Neurokinin 1 receptor antagonists), NK2R antagonists(Neurokinin 2 receptor antagonists)

Therapeutic Areas

Immune System DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Asthma

Originator Organization

Hoechst Marion Roussel, Inc.

Active Organization-

Inactive Organization

Hoechst Marion Roussel, Inc.

Drug Highest PhaseDiscontinuedDiscovery

First Approval Date-

Regulation-

Structure

Molecular FormulaC34H40Cl3N3O5

InChIKeyDAYXLOOGUORCMH-WAQYZQTGSA-N

CAS Registry167261-60-1

MDL 105,212 has been identified as a potent, nonpeptide NK-1 and NK-2 receptor antagonist that inhibits effects of substance P and neurokinin A in vitro and in vivo (Kudlacz et al., 1996). In the present study, the compound inhibited capsaicin-induced respiratory effects after p.o. administration (5-50 mg/kg) to conscious guinea pigs; nearly complete inhibition of dyspnea and cough was observed 1 hr after 50 mg/kg p.o., and efficacy persisted for approximately 11 hr. MDL 105,212 reduced pulmonary insufflation pressure and microvascular leakage in ovalbumin-sensitized animals in response to antigen-challenge relative to vehicle-treated animals. Attenuation of early-phase allergic responses may result from MDL 105,212 inhibition of antigen-induced histamine release from sensitized guinea pig lung observed in vitro. Airway hyperresponsiveness to methacholine occurred 24 hr after antigen-challenge in ovalbuminsensitized guinea pigs; this effect was inhibited by pretreatment with MDL 105,212 (50 mg/kg p.o.) 1 hr before ovalbumin exposure without affecting increased bronchoalveolar lavage eosinophil numbers. These data suggest that sensory neuropeptides play a role in some aspects of allergic airway responses and that tachykinin receptor antagonists may be useful in treatment of atopic respiratory diseases.

100 Deals associated with MDL-105212A

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