Disease relevance of DARODIPINE

• Objective evaluation of PY-108-068, a new calcium channel inhibitor for the treatment of chronic stable angina pectoris [1].
• Calcium antagonist (PY 108-068) treatment may further decrease flow in ischemic areas in acute stroke [2].
• In a model of cerebral vasospasm induced by autologous blood superfusion, PY 108-068 reversed the spastic state of cortical microvessels [3].
• Calcium antagonist PY 108-068: demonstration of its efficacy in various types of experimental brain ischemia [3].
• Exercise-induced asthma (expressed as maximal percent fall in the forced expiratory volume in one second from before baseline) was significantly attenuated only by 150 mg of PY 108-068 compared to placebo (24 +/- 13 vs 40 +/- 16; p less than 0.05) [4].

Psychiatry related information on DARODIPINE

• By contrast, acute administration of darodipine during the ethanol withdrawal phase was ineffective in reversing the withdrawal symptoms [5].

High impact information on DARODIPINE

• The calcium antagonist darodipine (10(-7) M) prevented the potentiation of the response to norepinephrine evoked by endothelin-1 [6].
• The effect of the possible influence of a new calcium antagonist, PY 108-068, on regional CBF was studied in patients suffering acute ischemic stroke [2].
• Resting blood pressure was reduced at the higher dose level but peak blood pressure during exercise and peak double product were unaltered by PY-108-068 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)[1]
• Unlike other calcium antagonists, treatment with PY-108-068 did not significantly alter the resting or maximal heart rates or the heart rate gain during exercise [1].
• The lowest concentration of darodipine did not affect action potential or twitch profile [7].

Biological context of DARODIPINE

• Darodipine (30 and 100 micrograms kg-1) attenuated the A II-induced vasoconstriction in the same vascular beds in rabbits as in cats including the kidneys, which were constricted after administration of the antagonist alone [8].
• Darodipine effected regional vasodilatation (measured with tracer microspheres) in the heart, brain and skeletal muscles as in cats [8].
• Elevation of the extracellular K+ concentration from 5.9 to 24 mM resulted in a significant reduction in negative inotropic IC50 values for Ro 18-3981 (137 fold), darodipine (8 fold) and nifedipine (20 fold) [9].
• Nifedipine and PY 108-068 increased cardiac output and heart rate, whereas verapamil only did so at high doses [10].
• These observations suggest that PY 108-068 can interact with its binding sites also in vivo [11].

Anatomical context of DARODIPINE

• Effect of the binding of isradipine and darodipine to different plasma proteins on their transfer through the rat blood-brain barrier. Drug binding to lipoproteins does not limit the transfer of drug [12].
• We studied the effects of darodipine in isolated human epicardial coronary arteries and in isolated right ventricular trabecula obtained from the explanted hearts of patients undergoing cardiac transplantation [13].
• In addition, K+ stimulated 45Ca2+ uptake into synaptosomes prepared from the hippocampus was insensitive to Bay K 8644 and PY 108-068 in normal or Na+ free conditions [14].
• A 6-month treatment (from the 18th to the 24th month of life) with an oral daily dose of 10 mg/kg of darodipine restored in part the expression of 200 kDa-NF subunit immunoreactivity in the cerebellar cortex [15].
• We evaluated coronary vasodilator and cardiac effects of PY 108-068 on isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs [16].

Associations of DARODIPINE with other chemical compounds

• Cardiovascular effects of two new calcium antagonists, PY 108-068 and PN 200-110, in conscious spontaneously hypertensive rats [17].
• In a further group of rabbits which had been subjected to cervical vagotomy and beta-adrenoceptor blockade (propranolol 1 mg kg-1 i.v.) before the experiment, vasopressin still caused coronary constriction which was reversed by darodipine, but had no effect on myocardial contractile force and heart rate [18].
• In awake, renovascular hypertensive rats, darodipine nanocapsules lowered blood pressure when given orally or intramuscularly, and the initial fall in blood pressure was less marked than that observed with the same dose of darodipine dissolved in polyethylene glycol 400 (PEG) [19].
• PURPOSE: The binding interactions of binedaline, nicardipine and darodipine with lipoproteins (HDL, LDL, VLDL) were examined as a function of pH in order to evaluate the role of lipoprotein components and ligand protonation in the binding process [20].
• These data indicate that treatment with the dihydropyridine-type Ca2+ channel blocker darodipine is able to counter in part the age-related loss in the expression of NF protein in the rat cerebellar cortex [15].

Gene context of DARODIPINE

• Treatment of aged rats with darodipine for 6 months increased the percentage of immunoreactive Purkinje neurons and the intensity of calbindin D-28K immunoreactivity in the cytoplasm of Purkinje neurons [21].
• Interactions between darodipine or isradipine and the 5-HT1A receptor agonist 8-OHDPAT in rat brain [22].

Analytical, diagnostic and therapeutic context of DARODIPINE

• In a chronic stroke model (microsphere embolization in rats) PY 108-068 led to a significant reduction in mortality and in the severity of neurological symptoms, whereby the peroral efficacy of the drug could be demonstrated [3].
• Determination of brain tissue oxygenation with pO2 microelectrodes showed that PY 108-068 improved oxygen supply in the cortex of cats subjected to epicerebral arterial occlusion [3].
• In a double-blind, randomised crossover study in 6 patients with chronic stable angina, we compared the acute effects of a single oral dose of placebo with 25 mg and 50 mg of PY 108-068 [23].
• Plasma concentration and CNS effects of Ca antagonists darodipine and nimodipine after single-dose oral administration to healthy volunteers [24].
• One group was treated with a daily dose of 5 mg/Kg of darodipine, while the control group of SHR was treated with placebo [25].

References