Disease relevance of SL 75212

• Myocardial infarction after ophthalmic betaxolol [1].
• Betaxolol and stuttering [2].
• In this multicenter, double-blind, parallel study, the antihypertensive effects of betaxolol (20 mg once daily) and/or chlorthalidone (25 mg once daily) were analyzed in 186 patients with essential hypertension [3].
• The patient received betaxolol (20 mg day-1); during a second electrophysiologic study, the tachycardia could not be induced, and it did not occur spontaneously during a follow-up period of 14 months [4].
• In conclusion, betaxolol proved to be effective in the treatment of supraventricular tachycardia; for chronic treatment, a single oral dose (20 mg) seems to suffice [5].

Psychiatry related information on SL 75212

• In the present study, 16 patients with severe neuroleptic-induced akathisia successively received low doses of three beta-blockers--propranolol, sotalol, and betaxolol [6].
• Betaxolol also reduced nest-leaving, suggestive of an alpha-1 beta-1 receptor synergy [7].
• The effects on heart rate (HR) and physical activity of 1 week's treatment with three different beta-adrenoceptor antagonists (20 mg betaxolol (Lorex); 160 mg propranolol LA; or 100 mg atenolol daily) have been compared with placebo in a double-blind study of 12 normal men [8].
• By contrast, betaxolol (20 mg p.o.), a selective beta1-antagonist devoid of serotonergic affinity, affected neither REM sleep nor EEG power [9].
• Betaxolol in anxiety disorders [10].

High impact information on SL 75212

• Results showed an increase of 13% and 8% in mean peak flow rate and forced expiratory volume in 1 s (FEV1), respectively, when using betaxolol; and of 14% and 11% when using dipivefrine [11].
• We recruited 80 patients aged over 60 years, who were without a history of airways disease and already used timolol, into a randomised crossover study comparing the effects on spirometry and exercise tolerance of changing to betaxolol or dipivefrine therapy [11].
• In the present experiments using single doses of antagonists that appeared to block 60% of beta 2- or beta 1-adrenergic receptors, it was found that the selective beta 2 antagonist ICI 118,551 was without effect on engram spread, whereas the selective beta 1 antagonist betaxolol inhibited the spread for at least 3 months [12].
• Autoradiographic inhibition curves with betaxolol or ICI-118,551 demonstrated that both the sinoatrial node and the atrioventricular bundle had inhibition profiles similar to the surrounding myocytes (predominantly beta 1) but unlike the inhibition profiles of arterioles (predominantly beta 2) [13].
• To delineate the distribution of beta-receptor subtypes in myocytic and vascular components of the heart, we incubated transmural sections of canine left ventricle with [125Iodo]cyanopindolol and selected concentrations of the beta 1-selective antagonist betaxolol or the beta 2-selective antagonist ICI 118,551 [14].

Chemical compound and disease context of SL 75212

• Comparison of propranolol, sotalol, and betaxolol in the treatment of neuroleptic-induced akathisia [6].
• The dose-response curves of betaxolol and atenolol were compared in 140 patients with mild to moderate essential hypertension [15].
• Used topically in glaucoma and ocular hypertension, betaxolol 0.5% solution produces a reduction in intraocular pressure of between 13 and 30%, an effect comparable with that of ocular timolol [16].
• The physiological actions of betaxolol lead to reducing neurotoxic effects in ganglion cells, which are the most susceptible retinal neurons to glutamate-induced damages under ischemic and glaucomatous conditions [17].
• In a double-masked, randomized, controlled clinical trial, the authors evaluated the ocular hypotensive efficacy of twice-daily treatment with levobunolol (0.25 and 0.5%) and betaxolol (0.5%) in 85 patients with open-angle glaucoma or ocular hypertension [18].

Biological context of SL 75212

• Betaxolol (10(-7) M) reduced the density of radioligand binding sites by 44% in regions composed primarily of ventricular myocytes but by less than 5% in small coronary arterioles [14].
• Changes in supine systolic blood pressure (SSBP) from baseline to the end of the single-therapy phase were 10 mm Hg for the betaxolol and 16 mm Hg for the chlorthalidone group [3].
• Radionuclide ventriculography was performed on placebo and during clinical beta-blockade (heart rate, 50 to 60 beats per minute and less than or equal to 20% increase in heart rate over baseline during stage I treadmill exercise, Bruce protocol) with the oral, cardioselective beta-blocking agent, betaxolol [19].
• Substitution of amino acids 316 to 324 of the beta(1)-adrenoceptor with the equivalent alpha(1b)-adrenoceptor sequence did not result in up-regulation by betaxolol [20].
• Betaxolol kinetics in hypertensive children with normal and abnormal renal function [21].

Anatomical context of SL 75212

• The subtype-selective antagonists betaxolol (beta 1), practolol (beta 1), and zinterol (beta 2) compete for [125I]iodocyanopindolol-binding sites on intact myocytes in monophasic manners with dissociation constants of 46, 845, and 923 nM, respectively [22].
• When the effective refractory period of the A-V node could be determined it was increased by betaxolol, whereas no significant electrophysiologic effects were observed in the atrium, the ventricle or the accessory pathway [5].
• Inverse agonists, able to reduce basal intracellular cAMP levels, such as betaxolol and ICI118551, resulted in both increased plasma membrane receptor and increased diffuse intracellular staining [23].
• Effects of betaxolol on light responses and membrane conductance in retinal ganglion cells [17].
• CONCLUSIONS: Topically applied betaxolol was bioavailable to posterior ocular tissues, including the retina and optic nerve head, of patients with glaucoma and of normal cynomolgus monkeys [24].

Associations of SL 75212 with other chemical compounds

• Basal and d-amphetamine-induced GluR1 phosphorylation was reduced by propranolol, a general beta-adrenoceptor antagonist, and betaxolol, a beta1-antagonist, but not by (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI-118,515), a beta2-antagonist [25].
• The dose (5 mg, 10 mg, and 20 mg betaxolol; 25 mg, 50 mg, and 100 mg atenolol) was increased if the supine diastolic blood pressure remained greater than 90 mm Hg after 4 weeks at each level [15].
• The CAM beta2-adrenoceptor displayed higher affinity for the agonist isoprenaline than the wild-type receptor but not for the antagonist alprenolol or the inverse agonist betaxolol [26].
• Parallel intact cell binding studies with [(3)H]dihydroalprenolol confirmed up-regulation of the CAM beta(2)-adrenoceptor-GFP by betaxolol but failed to predict the optically monitored up-regulation produced by high concentrations of alprenolol [23].
• Here we show that, of several beta-adrenergic receptor-blocking drugs tested, only two, ICI 118551 and betaxolol, inhibit the basal signaling activity of the beta 2-adrenergic receptor, thus acting as negative antagonists [27].

Gene context of SL 75212

• Furthermore, the finding that retinal levels of BDNF mRNA are raised following topical betaxolol treatment shows that not only can this drug reach the retina but that it can also induce changes in expression of factors which are known, themselves, to provide neuroprotection to retinal neurones [28].
• Betaxolol inhibits extracellular signal-regulated kinase and P70S6 kinase activities and gene expressions of platelet-derived growth factor A-chain and transforming growth factor-beta1 in Dahl salt-sensitive hypertensive rats [29].
• However, when experiments were carried out on animals that had been treated with betaxolol after ischemia/reperfusion, the intensity of eNOS immunoreactivity decreased compared to the untreated ischemic retinas [30].
• CONCLUSIONS: In this small pilot series, a single nucleotide polymorphism at codon 389 in the beta1-AR seems to correlate with a response to betaxolol therapy in normal, nonglaucomatous volunteers [31].
• The effects of systemic 8-OH-DPAT on 5-HT release were blocked completely by systemic administration of the 5-HT/beta adrenergic receptor antagonist, (-)-propranolol, but not by the beta-1 adrenergic receptor antagonist betaxolol or the beta-2 adrenergic receptor antagonist ICI-118,551 [32].

Analytical, diagnostic and therapeutic context of SL 75212

• beta-Adrenergic receptor subtypes were localized and differentiated in rat kidney slices by in vitro autoradiography using the nonselective beta-antagonist [125I]iodocyanopindolol in the presence of the selective agents betaxolol (beta 1) and zinterol (beta 2) [33].
• An IV dose of 20 mg of betaxolol per 1.73 m2 body surface area (BSA) was followed by six daily oral doses [21].
• To test this statement, 12 patients with mild to moderate hypertension performed a submaximal exercise test during treatment with placebo and after 3 and 24 months of monotherapy with betaxolol, 20 to 40 mg daily [34].
• Sustained treatment of HEK293 cells stably expressing the constitutively active mutant (CAM) beta(2)-adrenoceptor-GFP with the inverse agonist betaxolol resulted in a marked up-regulation of the fusion protein that could be monitored by both fluorescence and immunoblotting of membrane fractions [23].
• PURPOSE: To measure the concentration of betaxolol in tissues of humans with glaucoma and normal monkeys after topical administration [24].

References