Disease relevance of alprenolol

• Effect of alprenolol on mortality among patients with definite or suspected acute myocardial infarction. Preliminary results [1].
• Influence of alprenolol on hemodynamic and metabolic responses to prolonged exercise in subjects with hypertension [2].
• The plasma concentrations of alprenolol and its metabolite 4-hydroxy-alprenolol and the inhibition of exercise tachycardia were studied for 7 hr after the alprenolol [3].
• Depolarised and diseased myocardium is more sensitive to alprenolol and the drug's membrane depressant actions may be significant in terminating arrhythmias in such tissue [4].
• The effects of IPC on calpain, alpha-fodrin, and LDH release were blunted by the application of the PKA inhibitor H89 or alprenolol during IPC, while transient stimulation of PKA with CPT-cAMP or isoproterenol before ischemia attenuated calpain activation, alpha-fodrin degradation, and markedly reduced LDH release (P<0.001) [5].

High impact information on alprenolol

• To identify directly and to quantitate these beta-adenergic receptors in human lymphocytes, (-) [3H] alprenolol, a potent beta-adrenergic antagonist, was used to label binding sites in homogenates of human mononuclear leukocytes [6].
• Beta 1-Adrenergic receptor proteins were extracted from turkey erythrocyte membranes with lauroyl sucrose and digitonin and purified by affinity chromatography on a column of alprenolol agarose Affi-gel 10 or 15 [7].
• (iii) Alprenolol, a beta-blocker with partial agonist properties at beta-ARs, behaved as a beta-AR agonist, and acutely reduced peak Raw value by 75.7% (P < 0.05); chronically, it did not alter Raw [8].
• Hybridoma cells bearing monoclonal antibody against the beta-adrenergic ligand alprenolol were used as an immunogen to raise monoclonal anti-idiotypic antibodies [9].
• (Minus) [3-H] alprenolol, a potent beta-adrenergic antagonist, was used to identify binding sites in a fraction of canine cyocardium [10].

Chemical compound and disease context of alprenolol

• The author describes the notions that led to initiation of controlled trials of long-term medication with antiarrhythmic drugs following myocardial infarction, and reviews reports of controlled trials with diphenylhydantoin, alprenolol, and procaine amide [11].
• Different effects of propranolol, alprenolol, sotalol, atenolol and metoprolol on serum T3 and serum rT3 in hyperthyroidism [12].
• Decreased plasma concentrations and clinical effects of alprenolol during combined treatment with pentobarbitone in hypertension [13].
• Propranolol, alprenolol, oxprenolol and pindolol increased the incidence of catalepsy compared to HAL alone [14].
• In a group of 37 patients with definite acute myocardial infarction (AMI) allocated to treatment with either alprenolol (n = 20) or placebo (n = 17) serial determinations of concentrations in serum of myoglobin (S-Mb), creatine kinase (S-CK), aspartate aminotransferase (S-ASAT) and lactate dehydrogenase (S-LDH) were performed [15].

Biological context of alprenolol

• Finally, the class of anti-alprenolol monoclonal antibodies represented by 2G9 had the lowest antagonist binding affinity of all (IC50 alprenolol = 1 X 10(-5) M), did not demonstrate ligand stereoselectivity, and did not recognize agonists [16].
• Here, we report that a single amino acid substitution (Phe412----Asn) in the seventh hydrophobic domain of the alpha 2 adrenergic receptor reduces affinity for the alpha 2 antagonist yohimbine by 350-fold and increases affinity for beta antagonist alprenolol by 3000-fold [17].
• These data demonstrate the genetic diversity of the antibody response to alprenolol, and illustrate the extensive flexibility of the immune system [18].
• Isoproterenol, a beta-agonist, promoted a 2-3-fold increase in the rate of receptor phosphorylation which was blocked by the beta-antagonists propranolol and alprenolol [19].
• The V region genes (VH and VL) used in the immune response of BALB/c mice to alprenolol, a synthetic beta-adrenergic ligand, were examined by Southern blot and nucleotide sequence analyses [18].

Anatomical context of alprenolol

• Identification of beta-adrenergic receptors in human lymphocytes by (-) (3H) alprenolol binding [6].
• As an additional control, pooled inguinal adipose tissue from adult male Sprague-Dawley rats was incubated with the same concentrations of alprenolol [20].
• A compound from another synthesis was shown be to effective in displacing specific [125I]iodocyanopindolol binding from neonatal rat cardiac myocyte membranes, with a dissociation constant of 13.8 nM, whereas native alprenolol had a dissociation constant of 1.3 nM [21].
• Electrophysiological effects of alprenolol on depressed canine myocardium [4].
• Fat cells from hypo- and hyperthyroid rats showed the same affinity (K = 1.4 X 10(10) M(-1) and binding capacity (N = 1.21 X 10(-13) mol/microgram DNA) toward alprenolol as those from normal animals [22].

Associations of alprenolol with other chemical compounds

• The alpha-adrenergic agonist phenylephrine (in the presence of the beta-adrenergic antagonist alprenolol) stimulated respiration and incorporation of [3H]glycerol and [32P] Pi into phosphatidylinositol of hamster brown fat cells in a concentration-dependent manner [23].
• The relationship between blood and muscle lactate was altered by alprenolol, indicating that alprenolol prevents lactate translocation from the muscle to the blood [24].
• R- and S-enantiomers of propranolol, penbutolol, and alprenolol were investigated for their ability to bind to human 5-HT1A wild-type and Asn386Val mutant receptors [25].
• The protein binding of two basic drugs, alprenolol and imipramine, and the acidic drug, naproxen, was determined in plasma obtained from 23 healthy subjects [26].
• Lymphocytes from most control subjects did not respond in vitro to bacampicillin, alprenolol, or quinidine [27].

Gene context of alprenolol

• Rat adipose tissue has been previously shown to express the beta 3-adrenoreceptor and lipolysis was increased in rat adipose tissue in the presence of alprenolol 10(-4) M and 10(-5) M [20].
• These effects did not seem to be related to the unselective beta-adrenoceptor antagonist property of (-)alprenolol, since combined pretreatment with the beta1- and beta2-adrenoceptor antagonists, metoprolol and ICI 118551, did not alter the effects of dizocilpine on startle behaviour [28].
• The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol [29].
• (-)Alprenolol (5-HT1A and 5-HT1B receptor antagonist) and the 5-HT3-receptor antagonist, ICS 205-930, were without an antagonistic effect [30].
• Receptor blockade studies with yohimbine and alprenolol revealed that both of the inhibitory components of cocaine's actions (i.e., adrenergic alpha 2- and serotonergic 5-HT1A-receptor effects, respectively) were more efficient in reducing the DOI-induced HTR in supersensitive mice compared to normosensitive animals [31].

Analytical, diagnostic and therapeutic context of alprenolol

• A double-blind study of alprenolol versus placebo was done in patients with definite or suspected myocardial infarction to show the effect of the drug on mortality-rate after a year of treatment in patients aged less than or equal to 65 and to study the tolerance of the drug by patients greater than 65 years of age [1].
• Ocular delivery of alprenolol, a beta-adrenergic antagonist, by site-specific bioactivation of its methoxime analogue results in significant and prolonged decrease of the intraocular pressure in rabbits after topical administration [32].
• Frozen sections of rat kidney were incubated in a solution of (-)alprenolol, washed, exposed to fluorescent (-)alprenolol antibodies (FAA) and then observed at a fluorescence microscope [33].
• Pooled human liver microsomes containing cytochrome P450 enzymes were trapped by an ultrafiltration membrane in a stirred flow-through chamber, and eight beta-blocker drugs including acebutolol, alprenolol, atenolol, metoprolol, oxprenolol, pindolol, propranolol, and timolol were flow-injected through the chamber along with the cofactor NADPH [34].
• Steady-state alprenolol concentrations were determined from the area under the plasma concentration-time curve during one eight-hour dosage interval after treatment for six weeks [35].

References