A POTENT NEW β₂‐ADRENOCEPTOR BLOCKING AGENT

Abstract

I (t-Butyl-amino-3-ol-2-propyl) oximino-9 fluorene is a new P2-adrenoceptor blocking agent with a pA2 of 9.23 ± 0.25 on isolated trachea.2 It provokes hypertension in normotensive rats and does not prevent arterial hypertension in SHR rats, although it does prevent the renin secretion normally induced by isoprenaline infusion.

Effects of beta 1‐adrenoceptor agonism on plasma renin activity in normal men.

“…On the other hand predominant 813-adrenoceptor blocking agents such as atenolol (Amery et al, 1976) and metoprolol (Lijnen et al, 1979) are able to inhibit the renin secretion. However, selective ,82-adrenoceptor blockers, have been shown to antagonize the secretion of renin provoked by isoprenaline and to be more powerful than non-selective and selective j1-adrenoceptor blockers in these experimental models (Weber et al, 1974;Imbs et al, 1977). The latter results together with the findings of the present study could indicate that ,81-adrenoceptors are either not at all or only to a minor extent involved in the modulation of the secretion of renin.…”

Role of 1,4-Benzothiazine Derivatives in Medicinal Chemistry

“…An oxypropanolamine side chain linked to an aromatic ring are the chemical features required for β-blocking activity. However, the alteration of these features as the intercalation of an imino group in the side chain does not abolish the interaction on β-adrenoceptors but can lead, in some cases, to potent β-antagonists [28,29]. To evaluate the effect caused by a different type of insertion of pharmacophore oxypropanolamine chain in the 1,4-BT moiety that possesses short-lived blood pressure reducing effects in experimental animals [30], 6-, 7-, 8-oxypropanolamine and 6-, 7-, 8-acetimidoyloxypropanolamine of 3,4-dihydro-3-oxo-2H-1,4-benzothiazine were prepared [31].…”

Presynaptic β‐adrenoceptors in rat atria: evidence for the presence of stereoselective β1‐adrenoceptors

“…These drugs differ by their selectivity: acebutolol and betaxolol are known as cardioselective P-blockers, nebivolol is a new compound still under investigation with a high affinity for the fl-adrenoceptor, as demonstrated by binding assays (affinity f1/f2 = 47) and in vitro studies (IC50 in guinea-pig isolated trachea is 288 times higher than in atria) (Janssen preclinical report). Two selective 2 adrenoceptor blocking agents were assayed: IPS 339 (Imbs et al, 1977) and ICI 118 551 (O'Donnell & Wanstall, 1980) and finally, two fl-adrenoceptor blocking drugs possessing partial agonist activity, practolol and pindolol, were also studied.…”