Disease relevance of BUPRANOLOL

• Radiographic investigation of the proposita revealed that completion of stress fractures was necessary for healing; maturation of incomplete fractures resulted in stable Looser zones [1].
• Osteomalacia was indicated by Looser zones in one patient and confirmed by histologic evidence in three patients [2].
• We would suggest that bupranolol might be useful for prevention or treatment of thrombosis [3].
• Twelve Looser zones and 17 healing bands of the ribs obtained from autopsy cases of Itai-itai disease were analyzed by bone histomorphometry [4].
• Apart from a recent spontaneous fracture of the clavicle, Looser lines and pseudofractures were noted in a finger, fibula and malleolus [5].

High impact information on BUPRANOLOL

• Epinephrine in the presence of the beta-adrenoceptor antagonist bupranolol (10(-6) M) elicited a positive inotropic effect through activation of alpha 1-adrenoceptors in rat and rabbit, whereas in dog ventricular myocardium, bupranolol abolished the positive inotropic effect of epinephrine [6].
• Moreover, lipid production can be inhibited significantly by the (beta) AR antagonist bupranolol [7].
• This effect was completely blocked after preincubation of the cells with 1 microM bupranolol, a nonspecific beta-adrenoreceptor blocker, or 100 nM SR59230a, a specific beta3-adrenoreceptor antagonist [8].
• The involvement of beta(3)-AR in the negative inotropic effect was confirmed by the pretreatment with bupranolol, a non-selective beta-AR antagonist, which fully abolished the effects of SR 58611A [9].
• CGP12177-induced lipolysis was antagonized in vitro by bupranolol, a beta-adrenergic antagonist potent on rodent beta3-adrenoceptors but not by nadolol, a beta1- and beta2-adrenoceptor antagonist [10].

Chemical compound and disease context of BUPRANOLOL

• Betablocking drugs in essential hypertension: transdermal bupranolol compared with oral metoprolol [11].
• Dl-propranolol and bupranolol correct the hypertension and the tachycardia of the debuffered dog, whereas oxprenolol has only an action on the heart rate [12].

Biological context of BUPRANOLOL

• The potencies of the bupranolol analogues to increase heart rate were correlated (r=0.91, P<0.05) with their affinities for beta(1)-adrenoceptor binding sites in rat brain cortex membranes labelled with [(3)H]CGP 12177 (in the presence of ICI 118,551) [13].
• Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir-type transdermal delivery systems [14].
• A reservoir-type transdermal delivery system (TDS) of bupranolol (BPL) was designed and evaluated for different formulation variables like gel reservoirs (made with anionic and nonionic polymers), rate controlling membranes and penetration enhancers on the drug release and in vitro skin permeation kinetics of the devices [14].
• Effects of topically applied bupranolol on the intraocular pressure. Effects on the untreated eye [15].
• The problem of tachyphylaxis is discussed in the treatment of glaucoma with bupranolol eye drops [16].

Anatomical context of BUPRANOLOL

• In human fat cells, CGP 12,177-mediated lipolytic effect was antagonized by bupranolol and CGP 20,712A [17].
• However, these conformational receptor changes are not accompanied by changes in receptor affinity, because the affinity estimates for K 105 and bupranolol did not differ for a variety of myocardial tissues (including ventricular beta-adrenoceptors labelled with 3H-(-)-propranolol] and trachea, not even for tracheal receptor subtypes [18].
• In this study, bupranolol and SR 59230A were further evaluated for their potential alpha-adrenoceptor mediated effects (i.e., agonist and/or antagonist properties) in rat intralobar pulmonary artery and compared with BRL 37344 and CL 316243 [19].
• An adenosine A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA) elicited a pronounced negative inotropic effect with the EC50 value of 0.69 mumol/l in the presence of a beta-adrenoceptor blocking agent bupranolol (0.3 mumol/l) in the isolated ferret papillary muscle [20].
• Pharmacological analysis of atypical beta-adrenoceptors in the guinea pig gastric fundus using the beta(3)-adrenoceptor antagonist bupranolol [21].

Associations of BUPRANOLOL with other chemical compounds

• The effects of bupranolol, a new beta-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known beta-blocker [3].
• This effect was inhibited by bupranolol, suggesting that the possible action of nebivolol on beta3-adrenoreceptor is involved in its vasodilating properties [22].
• The beta-adrenoceptor blocker bupranolol turned out to be a competitive inhibitor of the polymorphic cytochrome P450 CYP2D6 of which sparteine is a substrate [23].
• The enzyme catalysing bupranolol metabolism was CYP2D6: microsomes from a liver with the genetic enzyme deficiency did not metabolize bupranolol; in microsomes from livers containing the enzyme and 10 microM bupranolol, 5 microM quinidine caused a 72% inhibition of bupranolol metabolism [23].
• In the antagonist experiment, bupranolol (beta-antagonist, 10(-6) to 10(-5) M) and SR 58894A (beta3-antagonist, 10(-7) to 10(-5) M) caused a rightward shift of the concentration-relaxation curve for isoprenaline, but CGP-20712A (beta1-antagonist, 10(-9) to 10(-7) M) and ICI-118551 (beta2-antagonist, 10(-9) to 10(-7) M) did not [24].

Gene context of BUPRANOLOL

• In contrast to the murine beta 3-adrenergic receptor, both bupranolol and (-)-propranolol were partial agonists of the bovine receptor [25].
• However, its action on cyclic AMP production is inhibited by bupranolol, a beta1-3-adrenoreceptor antagonist, and S-(-)-cyanopindolol, a selective beta3-adrenoreceptor antagonist [22].
• The KM value for bupranolol was lower than that reported for any other substrate of CYP2D6 [26].
• The beta(1)-adrenoceptor antagonist CGP 20712 given in combination with the beta(2)-adrenoceptor antagonist ICI 118,551 (0.1 micro mol kg(-1) each) reduced the positive chronotropic action of the five bupranolol analogues without affecting that of CGP 12177 [13].
• We furthermore determined the affinity of bupranolol to subclassify atypical beta/beta3-adrenoceptor in rat oesophageal muscularis mucosae, because it is rich in atypical beta/beta3-adrenoceptor [27].

Analytical, diagnostic and therapeutic context of BUPRANOLOL

• Determination of carboxybupranolol, the major metabolite of bupranolol, in human plasma by high-performance liquid chromatography [28].
• Influence of supersaturation on the pharmacodynamic effect of bupranolol after dermal administration using microemulsions as vehicle [29].
• After oral administration of 200 mg bupranolol to healthy volunteers, the maximal plasma concentration was observed within 1.2 h but it only reached a level close to the Ki-value [30].
• The positive chronotropic effect of i.v. SR 58611 A (200 nmol kg-1) was reduced by pretreatment with beta-adrenoceptor antagonists [propranolol, nadolol, bupranolol or the beta3-adrenoceptor selective antagonist, SR 59230 A (2 mg kg-1 i.v.)] and suppressed after sinoaortic denervation (i.e. after removal of vagal tone to the heart) [31].
• However, bupranolol produces local anesthesia on the eye [16].

References