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

Turner, Dawn Louise, Ferrari, Nicolay, Ford, William Richard ORCID: https://orcid.org/0000-0002-8792-6169, Kidd, Emma Jane ORCID: https://orcid.org/0000-0001-5507-1170, Paquet, Luc, Renzi, Paulo and Broadley, Kenneth John ORCID: https://orcid.org/0000-0002-3339-2050 2010. TPI 1020, a novel anti-inflammatory, nitric oxide donating compound, potentiates the bronchodilator effects of salbutamol in conscious guinea-pigs. European Journal of Pharmacology 641 (2-3) , pp. 213-219. 10.1016/j.ejphar.2010.05.025

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Abstract

Inhaled corticosteroids are regularly co-administered with β2-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 (sGaw) 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 μM 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 salbutamol there was enhanced bronchodilatation. Addition of the NO-donor, SNAP (0.1 mM), to the budesonide/salbutamol combination, also improved the inhibition of histamine-induced bronchoconstriction. This study has shown that TPI 1020 potentiates the bronchodilator activity of salbutamol, and their combination lasted longer than either drug administered individually. Both the corticosteroid and NO-releasing activities of TPI 1020 appear to be required for the potentiation of salbutamol. Combination of TPI 1020 with a β2-adrenoceptor agonist may therefore be useful against acute bronchoconstriction episodes in asthma, and may offer an opportunity for reducing doses of inhaled β2-adrenoceptor agonists.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	TPI 1020; Salbutamol; Bronchodilatation; Budesonide; SNAP; ODQ; Conscious guinea-pig
Publisher:	Elsevier
ISSN:	0014-2999
Last Modified:	18 Oct 2022 13:04
URI:	https://orca.cardiff.ac.uk/id/eprint/12220

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