Drugs online research references
Biochem Pharmacol. 1994 Jul 5;48(1):101-9.
Vaninolol: a new selective beta 1-adrenoceptor antagonist derived from vanillin.
Wu BN, Hwang TL, Liao CF, Chen IJ.
Department of Pharmacology, Kaohsiung Medical College, Taiwan, Republic of China.
The beta-adrenoceptor blocking properties of vaninolol ((+/-)4-[4'-(2-hydroxy-3-tert-butyl-aminopropoxy)-3'-methoxyphenyl]- 3-buten-2-one), derived from vanillin, were first investigated under in vivo and in vitro conditions. Vaninolol (0.1, 0.5, 1.0 mg/kg, i.v.), as well as propranolol, produced a dose-dependent bradycardia response and a sustained pressor action in urethane-anesthetized normotensive rats. Vaninolol inhibited the tachycardia effects induced by (-)isoproterenol, but had no blocking effect on the arterial pressor responses induced by phenylephrine. These findings suggested that vaninolol possessed beta-adrenergic blocking activity, but was without alpha-adrenergic blocking activity. In isolated guinea-pig tissues, vaninolol antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)isoproterenol suggested that vaninolol was a beta-adrenoceptor competitive antagonist. The effect of vaninolol was more potent on the atria than on tracheal tissues, indicating it had some beta 1-adrenoceptor selectivity. On the other hand, the order of the hydrophilicity was atenolol >> vaninolol > propranolol. In addition, vaninolol had a mild direct cardiac depression at high concentrations and was without intrinsic sympathomimetic activity (ISA). Furthermore, binding characteristics of vaninolol and other beta-adrenoceptor antagonists were evaluated in [3H]dihydroalprenolol binding to guinea-pig ventricular membranes. The order of potency of beta-adrenoceptor antagonists in competing for the binding sites was (-)propranolol >> vaninolol > or = atenolol. In conclusion, vaninolol was found to be a selective beta 1-adrenoceptor antagonist with relatively low lipophilicity in comparison with propranolol, devoid of ISA, and had a mild myocardial depressant effect.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8043010&dopt=Abstract
J Cardiovasc Pharmacol. 1998 May;31(5):750-7.
A highly selective beta1-adrenergic blocker with partial beta2-agonist activity derived from ferulic acid, an active component of Ligusticum wallichii Franch.
Wu BN, Huang YC, Wu HM, Hong SJ, Chiang LC, Chen IJ.
Department of Pharmacology, Kaohsiung Medical College, Taiwan, Republic of China.
Short-term injection of ferulinolol (0.1, 0.5, and 1.0 mg/kg, i.v.) produced dose-dependent bradycardia responses in pentobarbital-anesthetized Wistar rats, whereas it had no significant effects on the blood pressure. Ferulinolol markedly inhibited the tachycardia effects induced by (-)isoproterenol but did not show any blocking effect on the arterial pressor responses induced by (-)phenylephrine. These findings clearly suggested that ferulinolol had a beta-adrenergic blocking activity; nevertheless, it did not involve an alpha-adrenergic blocking action. In isolated guinea pig tissues, ferulinolol competitively antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses. The parallel shift to the right of the concentration-response curve of (-)isoproterenol suggested that ferulinolol was a beta-adrenoceptor-competitive antagonist. The apparent pA2 values for ferulinolol on right atria, left atria, and trachea were 7.62 +/- 0.05, 7.54 +/- 0.01, and 6.28 +/- 0.11, respectively. Ferulinolol was more potent on the atria than on tracheal tissues, demonstrating that it possessed beta1-adrenoceptor selectivity. The intrinsic sympathomimetic activity (ISA) of ferulinolol and propranolol were determined on isolated atria and trachea from reserpine-treated guinea pig. Propranolol caused significantly negative inotropic and chronotropic effects at > or =1 microM, whereas ferulinolol possessed fewer cardiodepressant activities than propranolol. In reserpine-treated tracheal strips, ferulinolol produced dose-dependent relaxant responses, but propranolol was without effectiveness. Preincubating the preparations with ICI 118,551 (0.1, 1.0, and 10 nM), a beta2-adrenoceptor antagonist, significantly shifted the concentration-relaxation curves of ferulinolol to a region of higher concentrations. These results implied that ferulinolol had a partial beta2-agonist activity. Further, binding characteristics of ferulinolol and various beta-adrenoceptor antagonists were evaluated in [3H]CGP-12177 binding to rat ventricular or lung membranes. The Ki values of ferulinolol, atenolol, metoprolol, and (-)propranolol were 103, 262, 123, and 0.23 nM, respectively, in ventricular membranes, and 2,412, 7,539, 2,186, and 0.72 nM, respectively, in lung membranes. In conclusion, ferulinolol was found to be a highly selective beta1-adrenoceptor antagonist with partial beta2-agonist activity but was devoid of alpha-adrenoceptor blocking action.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9593075&dopt=Abstract
Am J Physiol. 1997 Oct;273(4 Pt 2):H1669-76.
Role of beta1- and beta2-adrenergic receptors in regulation of Cl- and Ca2+ channels in guinea pig ventricular myocytes.
Hool LC, Harvey RD.
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
The role of beta1- and beta2-adrenergic receptor stimulation in modulating adenosine 3',5'-cyclic monophosphate (cAMP)-regulated Cl- and Ca2+ currents was investigated with use of guinea pig ventricular myocytes. Activation of the Cl- current by the nonselective beta-receptor agonist isoproterenol (Iso) was not affected by the beta2-receptor antagonist ICI-118,551 (ICI), but it was blocked by the beta1-receptor antagonist atenolol. The inability of beta2-receptor stimulation to activate the Cl- current was confirmed by the lack of response to the selective beta2-receptor agonists salbutamol and zinterol. Responses to beta2-adrenergic receptor stimulation were also looked for in pertussis toxin (PTX)-treated myocytes because PTX increases the sensitivity of responses to Iso, and PTX has been reported to increase the responsiveness to beta2- but not beta1-receptor stimulation. PTX treatment increased the sensitivity of the Cl- current to activation by Iso in the presence of ICI, indicating that PTX increases beta1-receptor responsiveness. PTX treatment also resulted in the ability of salbutamol to activate the Cl- current. However, the response to salbutamol was blocked by atenolol but not by appropriate concentrations of ICI, suggesting that salbutamol was activating beta1-receptors. These results indicate that PTX treatment increases the sensitivity to beta1-receptor stimulation, without affecting beta2-responsiveness. To verify that the lack of response to beta2-receptor stimulation was not unique to the Cl- current, the effects of beta2-receptor agonists on the L-type Ca2+ current were also examined. The Ca2+ current was only affected by high concentrations of zinterol or salbutamol, and such responses were blocked by atenolol, but not by ICI, suggesting that activation of beta1-receptors was involved. These results indicate that beta1- but not beta2-adrenergic receptor stimulation plays an important role in modulating the cAMP-regulated Cl- and Ca2+ currents in guinea pig ventricular myocytes.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9362229&dopt=Abstract
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