ovalbumin and carmoterol

This study evaluated the bronchodilating activity of the beta(2)-agonist carmoterol and the muscarinic M(3)-antagonist tiotropium, given intratracheally alone or in combination in anaesthetized artificially ventilated normal and actively sensitized guinea-pigs. Carmoterol (0.3-100pmol) and tiotropium (10-1000pmol) were superfused (0.01ml/min) for 5min before challenges with acetylcholine (20mug/kg i.v.), histamine (10mug/kg i.v.) or ovalbumin (5mg/kg i.v.). Both compounds given alone were markedly active against all the challenges. Tiotropium resulted more effective towards cholinergic challenge and carmoterol was very potent against histamine and ovalbumin-induced reaction, being effective already at 1pmol. In the presence of tiotropium, the bronchodilating activity of carmoterol was significantly augmented. The ED(50) value of carmoterol on the acetylcholine challenge was reduced by about 10 and 28 times (0.1 and 0.3pmol of tiotropium), that on the histamine one by 4.5 and 13 times (1 and 3pmol of tiotropium) and that on the ovalbumin-induced one by 8 and 25 times (10 and 30pmol of tiotropium). A positive interaction was also evident when other parameters were evaluated. The histamine-induced release of thromboxane B(2) was markedly reduced (56%, P<0.001) by combining completely ineffective doses of the two drugs (0.3 and 3pmol for carmoterol and tiotropium, respectively). In ovalbumin-challenged animals the time to death, amounting in control animals to 7.2+/-0.9min, was dose-dependently prolonged up to achieve complete protection from death with combination of 1 and 30pmol of carmoterol and tiotropium, respectively. The favorable interaction between carmoterol and tiotropium can represent a good option in the control of bronchopulmonary diseases marked by an increase of airway resistances.

Topics: Acetylcholine; Adrenergic beta-2 Receptor Agonists; Airway Obstruction; Airway Resistance; Amphetamines; Animals; Bronchoconstriction; Bronchodilator Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Guinea Pigs; Histamine; Hydroxyquinolines; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Male; Ovalbumin; Quinolones; Scopolamine Derivatives; Survival Analysis; Thromboxane B2; Tiotropium Bromide; Treatment Outcome

Relaxant effects of the beta 2-selective adrenoceptor agonist TA-2005 on bronchoconstriction in the anesthetized guinea pig and cat were evaluated in comparison with other known beta 2-adrenoceptor agonists. The ED50 values of intravenously administered TA-2005, procaterol, formoterol, isoproterenol, salbutamol, and salmeterol to inhibit the histamine-induced bronchoconstriction of the guinea pigs were 0.024, 0.053, 0.056, 0.099, 0.23, and 2.00 micrograms/kg, respectively, and those in serotonin-challenged cats were 0.019, 0.037, 0.039, 0.042, 0.13, and 0.52 micrograms/kg, respectively, in the same increasing order. When guinea pigs were passively sensitized with anti-ovalbumin antiserum, the ED50 values of TA-2005, formoterol, procaterol, and isoproterenol to inhibit the antigen-induced bronchoconstriction were 0.09, 0.30, 0.65, and 7.0 micrograms/kg, i.v., respectively, while those of TA-2005, procaterol, formoterol, and salbutamol in actively sensitized animals were 0.24, 0.25, 1.40, and 23.0 micrograms/kg. When TA-2005 was administered by inhalation to guinea pigs or by the intraduodenal route to cats, it exhibited a long-lasting inhibitory effect comparable or superior to the effects of salmeterol and formoterol. These data indicate that, among the known beta 2-adrenoceptor agonists examined, TA-2005 exerts the most potent bronchodilating effects with a long duration of action in vivo, and its potency ratios to the other reference drugs were greater in antigen- than spasmogen-induced bronchoconstriction models.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Amphetamines; Animals; Bronchodilator Agents; Cats; Dose-Response Relationship, Drug; Female; Guinea Pigs; Histamine Antagonists; Hydroxyquinolines; Hypersensitivity; Injections, Intravenous; Male; Myocardial Contraction; Ovalbumin; Quinolones; Respiratory Function Tests; Serotonin