Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tachykinins substance P and neurokinin A (NKA) are present in sensory airway nerves and have been implicated in the pathogenesis of asthma. FK224 is a cyclopeptide tachykinin antagonist previously shown to inhibit both tachykinin NK-1 and NK-2 receptor mediated airway responses in guinea pigs. Inhaled FK224 protected against bradykinin-induced bronchoconstriction and cough in asthmatics. In this study we examined the reproducibility of the NKA challenge and the effect of inhaled FK224 on NKA-induced bronchoconstriction in 10 patients with stable asthma. On Day 1 baseline lung function and PC20 methacholine were determined. On Days 2 and 3 increasing doubling concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol/ml) were administered via inhalation, with intervals of 10 min. On both days NKA caused a concentration-dependent decrease in specific airways conductance (sGaw) and FEV1. Mean +/- SEM, log PC35, sGaw NKA (mol/ml) was -6.61 +/- 0.10 on Day 2 and -6.57 +/- 0.14 on Day 3 (not significant [NS]). On Days 4 and 5 FK224 (4 mg) or placebo (P) was administered via metered-dose inhaler 30 min before NKA challenge in a double-blind, crossover manner. The study medication was well tolerated. FK224 had no significant effect on baseline lung function. After P and FK224, NKA caused a comparable concentration-dependent bronchoconstriction. The mean +/- SEM log PC35 sGaw NKA (mol/ml) was -6.04 +/- 0.18 after P and -6.19 +/- 0.23 after FK224 (NS). In conclusion, inhaled FK224 had no effect on baseline lung function and offered no protection against NKA-induced bronchoconstriction in a group of mild asthmatic patients.
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PMID:The effect of inhaled FK224, a tachykinin NK-1 and NK-2 receptor antagonist, on neurokinin A-induced bronchoconstriction in asthmatics. 866 34

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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PMID:Effect of MDL 105,212, a nonpeptide NK-1/NK-2 receptor antagonist in an allergic guinea pig model. 893 Jan 78