Tracheal relaxing effects and β₂ adrenoceptor selectivity of S1319, a novel sponge‐derived bronchodilator agent, in isolated guinea‐pig tissues

Abstract

1 S1319 (4-hydroxy-7-[1-(1-hydroxy-2-methylamino)ethyl]-1,3-benzothiazol-2(3H)-one acetate), a novel non-catecholamine b-adrenoceptor agonist, has been compared with isoprenaline, salbutamol and formoterol for activity in vitro on a range of b-adrenoceptor containing preparations from guinea-pig. 2 S1319, like isoprenaline, salbutamol and formoterol, relaxed preparations of guinea-pig trachea (contracted by histamine) in a concentration-dependent manner. The relaxing activity of S1319 appeared to be more potent than that of isoprenaline and salbutamol, and similar to that of formoterol (pD 2 values of 10.58+0.03 vs 7.60+0.01, 7.50+0.01 and 10.52+0.04, respectively), and was blocked by the b 2 -adrenoceptor selective antagonist (ICI 118,551). The intrinsic activity of S1319 was close to 1.0. 3 In the b 1 -adrenoceptor containing preparations, guinea-pig right and left atria, a monophasic inotropic response of S1319 was observed. The pD 2 value of S1319 for left atrial and right atrial inotropism was 6.70+0.15 and 7.81+0.01, respectively. 4 The selectivity ratio (trachea/left atrial inotropism) of S1319, formoterol, salbutamol and isoprenaline was 8523, 284, 4.8 and 0.45, respectively. The relative selectivity ratio of S1319 was 18743, 1858 and 30 times greater than that of isoprenaline, salbutamol and formoterol, respectively. 5 Relaxant responses of guinea-pig trachea to S1319 declined rapidly when the agonist was washed from the tissues, with complete recovery within 30 min. The duration of action of S1319 was similar to that of isoprenaline and less than that of salbutamol and formoterol. 6 In summary, S1319, a sponge-derived b-adrenoceptor agonist, is a potent and selective b 2 -adrenoceptor agonist with a short-duration of action in isolated guinea-pig tracheas. Keywords: b 2 -Adrenoceptor agonist; tracheal smooth muscle relaxation; duration of action Abbreviations: ICI 118,551, erythro-(+)-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol; pD 1 , negative logarithm of ED 50 ; S1319, 4-hydroxy-7-[1-(1-hydroxy-2-methylamino)ethyl]-1,3-benzothiazol-2(3H)-one acetate.

Comparison of Enantiomers of SPFF, a Novel .BETA.2-Adrenoceptor Agonist, in Bronchodilating Effect in Guinea Pigs

“…In addition, functional experiments on guinea pig or other animal species in vivo or in vitro will be needed to confirm the selectivity of (Ϯ)-SPFF and its enantiomers, because the selectivity of agonists differs according to the animal species and experimental conditions used. 26) In agreement with the results of the study in vitro, in vivo experiments revealed subsequently that (Ϫ)-enantiomer exhibited more potent bronchodilation than (ϩ)-enantiomer. In particular, the potency of (Ϫ)-SPFF was equivalent to that of (Ϯ)-SPFF in the protective activity against a bronchospasm induced by histamine-acetylcholine aerosol, suggesting that the protective activity of (Ϯ)-SPFF might mainly reside in its (Ϫ)-enantiomer.…”

Effect of sugammadex and neostigmine on tracheal muscle: In vitro study

“…Generally, responses of the tracheal and bronchial smooth muscle tissues are similar due to common histoembryonic structure in many in vitro studies [8][9][10][11][12], so we tried to discuss the issue on this context. Neostigmine, as an anticholinesterase, has many side effects including bronchospasm, bradycardia, increase in secretions, accelerate peristalsis, residual block [5].…”

The effects of S1319, a novel marine sponge-derived β 2 -adrenoceptor agonist, on IgE-mediated activation of human cultured mast cells

“…Furthermore, S1319 (Fig. 1), a novel b 2 -selective agonist [22,23], inhibited the tryptase release at the same potency as isoproterenol and formoterol (Fig. 2) and the inhibitory effect of S1319 on the tryptase release was blocked by addition of propranolol (Table 2).…”

“…2) and the inhibitory effect of S1319 on the tryptase release was blocked by addition of propranolol (Table 2). Although isoproterenol is a non-selective b-adrenoceptor agonist and propranolol is a non-selective b-adrenoceptor antagonist, that formoterol, albuterol and S1319, which are highly selective b 2 -adrenoceptor agonists [23], inhibited tryptase release suggests that the inhibitory activity is mediated through b 2 -adrenoceptors. Furthermore, RT-PCR analysis of b-adrenoceptor mRNA indicated that only b 2 -adrenoceptors are present in HCMC (Fig.…”

“…S1319 (4-hydroxy-7-[1-(1-hydroxy-2-methylamino)ethyl]-1,3-benzothiazol-2(3H)-one acetate) (Fig. 1) is a potent b 2 -adrenoceptor agonist with a short duration of action on airways smooth muscle in vitro [22,23]. In the present study, we describe the effect of S1319 (racemate) as an inhibitor of IgE-induced mediator and cytokine release from HCMC, comparing with the non-selective b-adrenoceptor agonist, isoproterenol (R-isomer), the selective b 2 -adrenoceptor agonist, albuterol (racemate), and the selective and long-acting b 2-adrenoceptor agonist, formoterol (racemate).…”