Drugs online research references
Naunyn Schmiedebergs Arch Pharmacol. 1997 May;355(5):645-50.
A long-lasting hypotensive effect of topical diltiazem on the intraocular pressure in conscious rabbits.
Santafe J, Martinez de Ibarreta MJ, Segarra J, Melena J.
Departamento de Farmacologia, Facultad de Farmacia, Universidad del Pais Vasco, Paseo de la Universidad no 7, Vitoria, Spain.
The effect of calcium channel blockers on intraocular pressure and aqueous humor dynamics remains still controversial, although preliminary evidence suggests that these drugs may be beneficial in the management of ocular hypertension and low-tension glaucoma. Having previously reported the ocular hypotensive effect of topical nifedipine and verapamil in albino rabbits, the original aim of the present work was to evaluate the effect of topical diltiazem on aqueous humor dynamics in this species. Intraocular pressure was measured with a manual applanation tonometer. The experiments examining the ocular actions of diltiazem were carried out in two stages. In the first one, short term effects of topical diltiazem on intraocular pressure were studied in groups of 13 albino rabbits receiving 8 different doses of the drug in order to obtain a dose-response curve. Tonographies were performed in 13 anaesthetized animals before and 90 min after drug instillation. In a second phase, the persistence of the effect of diltiazem on intraocular pressure was examined in 6 groups of 10 rabbits each receiving three different doses of the drug. Topical diltiazem was found to lower intraocular pressure in a dose-related fashion. The maximum response to diltiazem was greater and the ED50 lower than those previously reported for nifedipine and verapamil. In the tonographic study, diltiazem was shown to reduce the facility of aqueous humor outflow and inflow. Diltiazem exhibited a long lasting effect on intraocular pressure that was again dose-related. Depending on the dose administered, the calculated time necessary for the peak effect to be halved ranged from 0.6 to 7.0 days. Due to the intensity and the persistence of its intraocular pressure-lowering effect, diltiazem shows great potential for the treatment of glaucoma, since a daily or less frequent administration may be enough to control ocular hypertension.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9151305&dopt=Abstract
Hypertension. 1997 Nov;30(5):1169-74.
Vasodilators, aortic elasticity, and ventricular end-systolic stress in nonanesthetized unrestrained rats.
Niederhoffer N, Marque V, Lartaud-Idjouadiene I, Duvivier C, Peslin R, Atkinson J.
Laboratoire de Pharmacologie Cardio-vasculaire, Faculte de Pharmacie de l'Universite Henri Poincare, Nancy I, France.
We evaluated the effect of different vasodilators on ventricular end-systolic stress by investigating the impact of sodium nitroprusside, nifedipine, and hydralazine on blood pressure, aortic stiffness, and wave reflection during drug-induced hypotension (to 80 mm Hg mean blood pressure) in normotensive (central aortic mean blood pressure, 116 to 119 mm Hg; systolic pressure, 133 to 137 mm Hg), nonanesthetized, unrestrained rats. Aortic stiffness was evaluated from the slope of the linear regression relating pulse wave velocity (PWV) to central aortic mean or pulse pressure. The fall in central aortic systolic blood pressure was less than the fall in mean pressure, especially after hydralazine (122+/-4 mm Hg; sodium nitroprusside, 107+/-2; and nifedipine, 112+/-3 mm Hg; P<.05). The PWV/mean pressure slope was linear, positive, and similar in all three groups (hydralazine, 3.3+/-0.2; sodium nitroprusside, 3.8+/-0.3; and nifedipine, 3.9+/-0.3 cm x s[-1]x mm Hg[-1]; P>.05). The PWV/pulse pressure slope was linear, negative, and less steep in the case of hydralazine (-4.9+/-0.6; sodium nitroprusside, -15.5+/-3.7; and nifedipine, -13.5+/-2.9 cm x s[-1] x mm Hg[-1]; P<.05). The travel time and augmentation index of the reflected wave were similar in all groups. In conclusion, sodium nitroprusside and nifedipine had a more beneficial effect on end-systolic stress than did hydralazine. This does not appear to be related to any specific effect on wave reflection or the "static" relationship between PWV and aortic mean blood pressure; it may be related to the effects of these drugs on the "dynamic" relationship between PWV and pulse pressure.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9369272&dopt=Abstract
Eur J Pharmacol. 2000 Jun 30;399(1):65-73.
Effects of phorbol 12,13-diacetate on human isolated bronchus.
Sarria B, Pedros C, Galan G, Cortijo J, Morcillo EJ.
Department of Pharmacology, Faculty of Medicine, University of Valencia, Avenida Blasco Ibanez 15, E-46010, Valencia, Spain.
Protein kinase C appears to be involved in the regulation of airway contractility. Phorbol 12,13-diacetate (PDA; 0.01-10 microM), a protein kinase C activator, produced a transient relaxation followed by a sustained contraction of human isolated bronchus. Different protein kinase C inhibitors (calphostin C, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine) (H-7), nifedipine (NIF; 1 microM) or incubation with Ca(2+)-free medium, inhibited the spasmogenic response to phorbol, while ouabain (10 microM) suppressed only the initial relaxation. These results indicate that the initial relaxation, in response to PDA, is related to the activation of Na(+)/K(+)-ATPase, while the ensuing contraction depends on extracellular Ca(2+) entry.Incubation with PDA (1-5 microM) depressed the maximal relaxation to theophylline and caffeine obtained at 37 degrees C but augmented the spasmogenic responses to methylxanthines (10 mM) obtained in cooled preparations. These effects do not result apparently from increased extracellular entry of Ca(2+), but instead, from facilitation of the release of Ca(2+) from intracellular stores.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10876024&dopt=Abstract
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