Studies on the interaction between formoterol and salmeterol in guinea-pig trachea in vitro.
The actions of and interaction between formoterol and salmeterol were studied on guinea-pig trachea in vitro. Tracheal strip preparations were contracted by 1 mumol/l carbachol giving a near maximal contraction. Salmeterol in concentrations from 0.1 to 3 mumol/l relaxed the tracheal smooth muscle by about 30 per cent of the maximum relaxation produced by theophylline. Formoterol caused a concentration-dependent and almost complete relaxation with a pD2 of 8.56. In the presence of salmeterol there was a rightward shift of the concentration-response curve for formoterol. The pA2 for salmeterol was estimated to 7.42. Similar experiments with isoprenaline indicated that salmeterol has a low affinity for beta 1-adrenoceptors. Formoterol and salmeterol both inhibited in a concentration-dependent manner the contractions evoked by stimulation of the vagus nerve in a tracheal tube preparation. The degree of inhibition decreased with increasing stimulation frequency. Complete inhibition was attained with salmeterol, but not with formoterol, at the highest frequency employed (45 Hz). The inhibiting effect of 10 mumol/l salmeterol was not blocked by 10 mumol/l sotalol, a beta-adrenoceptor antagonist. It is concluded that salmeterol, in comparison to formoterol, is a partial beta 2-adrenoceptor agonist and has, at high concentrations, an additional unspecific inhibitory action.
Department of Pharmacology 2, Astra Draco AB, Lund, Sweden.
A B
AB
Jeppsson
B L
BL
Källström
B
B
Waldeck
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004594:Electrophysiology; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects*; D000068299:Salmeterol Xinafoate; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate