Drugs online research references
Pharmazie. 1993 Sep;48(9):690-4.
Hemodynamic response and effects on myocardial energetics of 3-cyano-2-morpholino-5-(pyrid-4-yl)pyridine (AWD 122-14) in anesthetized minipigs.
Rohde E, Wiesner B, Muschick P.
Research Institute of Molecular Pharmacology, Berlin.
AWD 122-14, a new positive inotropic and vasodilating agent, was investigated in comparison to amrinone, milrinone and dopamine in anesthetized minipigs. AWD 122-14 (1.17.10(-7)-37.5.10(-7) mol/kg) increased dose-dependent left ventricular contractility (LV dp/dtmax) (122x5 +/- 11x3%; ED50 = 8.1x10(-7) to mol/kg). Dopamine (2.64x10(-8)-21x12 x 10(-8) mol/kg) in comparison increased contractility up to 153.1 +/- 44.9% of control value and is about 20 times more potent than AWD 122-14 at the ED50 value and about 10 times more potent at the ED30 value. Amrinone (1.60x10(-6)-16.90x10(-6) mol/kg) and milrinone (1.48x10(-7)-23.70x10(-7) mol/kg) only slightly increased contractility in anesthetized minipigs, but they appear to posses a similar pharmacological profile like AWD 122-14. The hemodynamic effects were associated with an increase in myocardial oxygen consumption (E1: 18.8 +/- 10.0%) due to the marked increases in LV dp/dtmax and heart rate. LVMW was unchanged and LVSW decreased (-29.0 +/- 10.2%) after application of AWD 122-14. The reduction in left ventricular work (LVMW, LVSW) and the increase in myocardial oxygen consumption led to a decrease of left ventricular external mechanical efficiency of the non-failing minipig heart (Etam: -21.1 +/- 9.4%). Additional hemodynamic effects of AWD 122-14 were studied under calcium channel blockade (verapamil, nifedipine). After pretreatment with verapamil the agent (1.17.10(-7)-18.75.10(-7) mol/kg i.v.) increased left ventricular contractility between 42.9 +/- 41.6% and 58.5 +/- 33.3%. After pretreatment with nifedipine the agent induced a dose-dependent increase in LV dp/dtmax between 11.1 +/- 7.7% and 47.8 +/- 23.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8234405&dopt=Abstract
Pharmacol Biochem Behav. 1996 Sep;55(1):93-8.
Behavioral and analgesic effects induced by administration of nifedipine and nimodipine.
Martin MI, del Val VL, Colado MI, Goicoechea C, Alfaro MJ.
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Evidence exists that calcium antagonists can have effects on neural function. The aim of this work is to analyze the effect of two dihydropyridines, nifedipine and nimodipine, administered for 11 days on the behavior and pain sensitivity of rats. Nociception was tested using the tail electric stimulation test, and behavior parameters using a holeboard. Our results show that chronic administration of nifedipine or nimodipine induces analgesia that can be evaluated by tail withdrawal. However, neither the vocalization nor the vocalization after discharge were modified, so the analgesia may be mediated by spinal mechanisms. Rats treated with nifedipine or nimodipine exhibited a dose-dependent tendency to avoid the center of the field without modification of other parameters, suggesting an increased emotivity in the rats. This conclusion is supported by the fact that anxiogenic or anxiolytic drugs modify the pattern of locomotion without significant changes in other parameters related with the motility. The results from this study suggest the view of a complex mechanism of action underlying nifedipine- and nimodipine-mediated behavioral effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8870043&dopt=Abstract
Pharmacol Toxicol. 1997 Jun;80(6):262-5.
Comparative study on the effect of calcium channel blockers on basal and parathyroid hormone-induced bone resorption in vitro.
Redlich K, Pietschmann P, Stulc T, Peterlik M.
Department of General and Experimental Pathology, University of Vienna Medical School, Wien, Austria.
A number of clinical and experimental studies suggest that the effects of calcium channel blockers are not limited to the cardiovascular system but might also involve skeletal calcium metabolism due to the presence of L-type calcium channels in osteoblastic cells. We therefore investigated the influence of calcium channel blockers of the dihydropyridine type (nifedipine, amlodipine) as well as of the phenylalkylamine type (verapamil, gallopamil) on basal and parathyroid hormone-induced bone resorption utilizing organ-cultured neonatal mouse calvaria. Only at 10(-4) M, amlodipine, verapamil and gallopamil reduced basal and parathyroid hormone-induced resorption In contrast, nifedipine, between 10(-5)-10(-4) M, exhibited a dose-dependent inhibitory effect on parathyroid hormone-related bone resorption by up to 50%. When calvariae were cultured for 48 hr in the presence of inhibitory concentrations of the calcium channel blockers and then stimulated with parathyroid hormone, only parietal bones pretreated with nifedipine remained completely responsive to the bone resorbing action of the hormone.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9225361&dopt=Abstract
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