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Abstract

Effect of MDL 105,212, a nonpeptide NK-1/NK-2 receptor antagonist in an allergic guinea pig model.

E M Kudlacz, R W Knippenberg, D E Logan and T P Burkholder
Journal of Pharmacology and Experimental Therapeutics November 1996, 279 (2) 732-739;
E M Kudlacz
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R W Knippenberg
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D E Logan
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T P Burkholder
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Abstract

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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 279, Issue 2
1 Nov 1996
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Abstract

Effect of MDL 105,212, a nonpeptide NK-1/NK-2 receptor antagonist in an allergic guinea pig model.

E M Kudlacz, R W Knippenberg, D E Logan and T P Burkholder
Journal of Pharmacology and Experimental Therapeutics November 1, 1996, 279 (2) 732-739;

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Abstract

Effect of MDL 105,212, a nonpeptide NK-1/NK-2 receptor antagonist in an allergic guinea pig model.

E M Kudlacz, R W Knippenberg, D E Logan and T P Burkholder
Journal of Pharmacology and Experimental Therapeutics November 1, 1996, 279 (2) 732-739;
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