TPI 1020, a novel anti-inflammatory, nitric oxide donating compound, potentiates the bronchodilator effects of salbutamol in conscious guinea-pigs

European Journal of Pharmacology
D l TurnerK J Broadley

Abstract

Inhaled corticosteroids are regularly co-administered with beta(2)-adrenoceptor agonists. This study evaluates in conscious guinea-pigs the bronchodilator effect, alone or combined with salbutamol, of TPI 1020, a novel anti-inflammatory corticosteroid and nitric oxide (NO) donor derived from budesonide. Guinea-pigs received inhaled histamine (3 mM) and specific airway conductance (sG(aw)) measured. Responses to histamine were measured before and on the next day 15 min after a 15 min inhalation of vehicle, salbutamol, TPI 1020, budesonide, the NO-donor, S-nitroso-N-acetylpenicillamine (SNAP), or combinations of these drugs. Salbutamol and TPI 1020 caused concentration-dependent bronchodilatation measured as inhibition of histamine-induced bronchoconstriction. TPI 1020-induced bronchodilatation was blocked by the guanylyl cyclise inhibitor, ODQ, indicating cGMP-dependence through released NO. While salbutamol at 80 microM did not exert significant bronchodilatation, significant inhibitions were observed when co-administered with TPI 1020, 0.11 and 0.33 mM. The combined effects of TPI 1020 and salbutamol lasted significantly longer than either drug alone. Inhaled budesonide was a weak bronchodilator and when co-administered with s...Continue Reading

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Citations

Jan 1, 2011·ISRN Allergy·Carla M PradoIolanda F L C Tibério
Jun 18, 2017·Breathe·Mukhallad AljanabiNayef S Gharaibeh
May 23, 2012·Pharmacological Reviews·Mario CazzolaM Gabriella Matera
Sep 29, 2020·Journal of Experimental Pharmacology·Paola RoglianiLuigino Calzetta
Dec 19, 2020·Pulmonary Pharmacology & Therapeutics·Tidarat SriboonyongHarutai Kamalaporn

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