Pulmonary pharmacology & therapeutics
-
Pulm Pharmacol Ther · Jan 2002
ReviewDelta-opioid receptor antagonists as a new concept for central acting antitussive drugs.
Our recent findings indicated that mu- and kappa-opioid receptors enhance each other's antitussive processes. However, delta-opioid receptors played an inhibitory role in antitussive processes mediated by the mu- and kappa-opioid receptors. ⋯ These delta-opioid receptor-mediated antitussive effects may be mediated by the antagonism of delta(1)-, but not delta(2)-opioid receptors. In this review, we study the possibility of the delta-opioid receptor antagonist as a new concept for central acting antitussive drugs.
-
Pulm Pharmacol Ther · Jan 1999
Randomized Controlled Trial Clinical TrialPharmacokinetics and pharmacodynamics of cumulative single doses of inhaled salbutamol enantiomers in asthmatic subjects.
Objectives of this study were to compare the pharmacokinetics, pharmacodynamics and safety of single cumulative doses of active (R)-salbutamol given either as the single enantiomer or racemic mixture by inhalation to subjects with mild to moderate asthma. This was a double-blind, crossover, cumulative-dose, randomized study where all subjects received either four doses of 1.25 mg of (R)-salbutamol or 2.5 mg of racemic (RS-) salbutamol by nebulization. The pharmacokinetic parameters were determined by noncompartmental analysis and model-fitting. ⋯ All pharmacodynamic parameters were similar whether (R)- or (RS)-salbutamol was given. The exposure to (R)-salbutamol was identical after inhalation of (R) -and (RS)-salbutamol by subjects with asthma. Several pharmacological responses including FEV(1)were also similar and there were no unique safety concerns with either treatment.
-
Pulm Pharmacol Ther · Feb 1998
Characterization of tachykinin receptors mediating bronchomotor and vasodepressor responses to neuropeptide gamma and substance P in the anaesthetized rabbit.
The effects of i.v. injections of two endogenous tachykinins, substance P (SP) and neuropeptide gamma and the highly selective tachykinin agonists [Sar9,Met(O2)11]-SP, [Lys5,MeLeu9, Nle10]-NKA(4-10) and senktide, on total lung resistance (RL), dynamic lung compliance (Cdyn) and systemic blood pressure, were compared in the anaesthetized rabbit. Senktide, the NK-3 receptor selective agonist, had no effect on RL, Cdyn or blood pressure. The other four agonists caused dose-dependent increases in RL and Cdyn, with [Sar9,Met(O2)11]-SP being the most potent agonist in producing changes in the absence of phosphoramidon. ⋯ In the presence of phosphoramidon, the non-peptide tachykinin NK-1 receptor selective antagonist CP 96345 (80 nmol/kg) reduced all responses to [Sar9,Met(O2)11]-SP and SP, whereas the NK-2 selective antagonist SR 48968 (40 nmol/kg) inhibited the bronchomotor but not the vasodepressor responses to neuropeptide gamma and [Lys5,MeLeu9, Nle10]-NKA(4-10). The fall in blood pressure induced by neuropeptide gamma was diminished by CP 96345, whereas bronchoconstriction was unaffected, indicating possible differences in NK-1 receptors in the vasculature and airways. Electrical stimulation of the distal ends of vagus nerves caused increases in RL which were abolished by atropine (1 mg/kg).
-
Pulm Pharmacol Ther · Jan 1997
Comparative Study Clinical TrialRecombinant human DNase (rhDNase) influences phospholipid composition, surface activity, rheology and consecutively clearance indices of cystic fibrosis sputum.
Cystic fibrosis (CF) is caused by mutation in the gene for the CF transmembrane conductance regulator which leads to massive, abnormally viscous, purulent sputum, chronic destructive endobronchitis and early death. Purified recombinant human (rh) DNase can digest extracellular DNA and its inhalation in these patients significantly improves lung function. To evaluate the poorly understood mechanisms, saliva protected sputum from patients treated with and without rhDNase were evaluated. ⋯ The rigidity was significantly lower and the ratio of viscosity in proportion to elasticity increased. All these data are consistent with an increased clearability of the sputum by coughing, but not by mucociliary activity. Thus the interaction of inhaled rhDNase with the purulent mucus and the endobronchial inflammatory processes may induce changes that result in rheological properties favoring clearance of sputum by cough.