Beta-agonistic properties of tulobuterol, a new beta-sympathicomimetic drug, and its effects on pulmonary beta-adrenoceptor characteristics.

Radioligand binding studies have been developed to determine pharmacologic receptor characteristics in vitro. With this assay, not only the number and dissociation constant (KD) can be studied, but also the interaction of agonists with the receptor. We used this method to study a new beta 2-sympathicomimetic drug, tulobuterol (1-(0-chlorophenyl)-2-butylamino-ethanol hydrochloride). Two sets of experiments were performed. One set of experiments investigated the effects of tulobuterol and terbutaline in chronic administration, while the second set compared the beta-adrenoceptor-stimulating properties of tulobuterol with terbutaline and salbutamol. The effects of 10 days' administration of tulobuterol and terbutaline on beta-adrenergic characteristics in rats were assessed biochemically by means of radioligand binding studies on pulmonary membranes and functionally using isolated tracheal spirals. It was found that: (1) In vivo treatment with both drugs induced a reduction of the number of beta-adrenoceptors bound by 3H-dihydroalprenolol (3H-DHA); however, tulobuterol also induced an increased affinity for beta-adrenoceptor binding. (2) Tulobuterol induced a significant increase in the sensitization of tracheal smooth muscle, facilitating the relaxation of airway smooth muscle. The inhibition of 3H-DHA binding with the three drugs was best fit in a two-binding site model, showing high- and low-affinity binding sites. The high-affinity sites had similar KD values for terbutaline and tulobuterol (1.6 x 10(7) and 1.5 x 10(-7), respectively). The high-affinity sites for salbutamol had a higher KD value (9.4 x 10(-7), suggesting a lower affinity.(ABSTRACT TRUNCATED AT 250 WORDS)