Drugs online research references
Klin Wochenschr. 1985 Nov 15;63(22):1170-3.
Kinetics of 1,2-dinitroglycerin following sustained release nitroglycerin: influence of propranolol and metoprolol.
Ochs HR, Verburg-Ochs B, Greenblatt DJ.
Ten healthy volunteers ingested a single 18-mg oral dose of sustained release nitroglycerin (TNG) (Giulini-Pharma) on three occasions: once in the control state, once during coadministration of propranolol (80-mg three times daily), and once during coadministration of metoprolol (100-mg twice daily). The degree of beta adrenergic blockade was evaluated by the metaproterenol infusion test. Plasma concentration of TNG and its major metabolite, 1,2-dinitroglycerin (DNG), during 12 h after each dose were measured by gas chromatography-mass spectrometry. Intact TNG was not detected in the plasma of any patient. The major metabolite, DNG, was easily measurable in blood, and had a biphasic plasma concentration profile. Coadministration of the beta-blockers had no influence on any of the kinetic variables for DNG. The mean values during control, propranolol, and metoprolol trials of DNG elimination half-life were: 1.35, 1.10, and 1.09 h; total area under the curve: 42, 38, and 42 ng/ml X h; oral clearance: 6.6, 7.2, and 6.4 liters/min. Thus TNG when administered as a sustained release oral preparation is rapidly and completely transformed to DNG. There was no pharmacokinetic interaction between sustained release TNG and two commonly used beta-blocking agents, suggesting that any clinical interaction that may-occur between sustained release nitroglycerin and beta-blocking agents is pharmacodynamic rather than pharmacokinetic in nature.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3935852&dopt=Abstract
J Appl Physiol. 1986 May;60(5):1722-6.
Effects of beta 1- vs. beta 1- beta 2-blockade on training adaptations in rat skeletal muscle.
Thomas DP, Jenkins RR.
The effect of selective vs. nonselective beta-blockade on fast-twitch [extensor digitorum longus (EDL)] and slow-twitch [soleus (SOL)] muscle enzyme activities following endurance training were characterized. Citrate synthase (CS), lactate dehydrogenase (LDH), and beta-hydroxyacyl-CoA dehydrogenase (HAD) activities were compared in SOL and EDL muscles of trained (T), metoprolol-trained (MT), propranolol-trained (PT), and sedentary (C) rats. Following 8 wk of treadmill running (1 h/day, 5 days/wk at approximately 30 m/min), LDH activity was depressed approximately 20% (P less than 0.05) in both SOL and EDL in only the PT rats, indicating inhibition of beta 2-mediated anaerobic glycolysis. EDL CS activity was similarly elevated in all three trained groups compared with sedentary controls. In SOL muscle, however, a drug attenuation effect was observed so that CS activity was increased only in the T (P less than 0.01) and MT (P less than 0.05) groups. HAD enzyme activity was increased somewhat (P less than 0.10) in SOL muscle in only the T group, but more so (P less than 0.05) in EDL in all three trained groups. The above findings suggest a training-induced selectivity effect not only with respect to beta 1-vs. beta 1-beta 2-blockers, but also with respect to muscle fiber type.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2872198&dopt=Abstract
J Pharm Pharmacol. 1991 Jul;43(7):504-9.
Cardiovascular effects of intracerebroventricular injections of (+/-)-nebivolol and its enantiomers--a comparison with those of metoprolol in the rat.
Midol-Monnet M, Davy M, Heimburger M, Beslot F, Cohen Y.
Laboratoire de Pharmacologie, Faculte de Pharmacie, URA-CNRS 594, Chatenay-Malabry, France.
The cardiovascular effects of (+/-)-nebivolol, a potent beta 1-adrenoceptor antagonist, and its enantiomers, (+)-nebivolol (SRRR) and (-)-nebivolol (RSSS) in normotensive anaesthetized rats, have been investigated using metoprolol as a reference substance. The drugs decreased blood pressure and heart rate immediately after i.c.v. injection. These effects paralleled the beta-blocking potencies ((+)- greater than (+/-)-greater than (-)-nebivolol). Metoprolol induced a weaker hypotension than (+/-)-nebivolol, and a long-lasting reduction in stroke volume. As reported after i.v. administration, (+/-)-nebivolol and isomers by the i.c.v. route decreased peripheral vascular resistance following i.c.v. administration while metoprolol increased it. These effects are centrally mediated since cardiovascular responses to isoprenaline i.v. remained unchanged.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1682465&dopt=Abstract
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