1) Daily dose was 10-20mg Q.D. for 12 weeks. 2) Mean systolic and diastolic pressure were decreased by 49mmHg(25.9%), and 18mmHg(16.8%) respectively. But there was no significant change in heart rate before and after treatment. 3) Systolic and diastolic blood pressure were stably maintained on the whole day. 4) There were no significant side effects except two cases of aggravated congestive heart failure and hypertension. 5) There were no significant changes on hematologic & biochemical parameters before and after treatment.
Blood Pressure ; Heart Failure ; Heart Rate ; Hypertension ; Nitrendipine*

Fifty patients with mild essential hypertension were studied to evaluate the efficacy of once-daily regimen of nitrendipine, 10~20mg daily for 12 weeks. 1) Thirty-Seven patients completed the study and showed -9% change in mean arterial headache etc. 2) Eight patients were dropped out because of side reaction, namely flushing, palpitation, headache etc. 3) Ambulatory blood pressure monitoring before and after treatment in 3 patients confirmed the drug efficacy revealing 9% decrement in mean blood pressure and 46% decrease in % elevated BP. 4) Twenty patients who were controlled with other hypotensive drugs were well controlled & maintained the blood pressure in normal range after switching to nitrendpine 10~20mg daily. In conclusion, citrendipine is a safe and good antihypertensive calcium antagonist in the treatment of mild hypertensives with 10~20mg of once-daily dosage.
Blood Pressure Monitoring, Ambulatory ; Blood Pressure* ; Calcium ; Flushing ; Headache ; Humans ; Hypertension ; Nitrendipine* ; Reference Values

AIMTo prepare the sustained-release nitrendipine microspheres with a solid dispersed structure in liquid system.

METHODSThe sustained-release nitrendipine microspheres with a solid dispersed structure was prepared in liquid system by combining spherical crystallization technique and solvent deposition method in one step. The resultant microspheres were evaluated for the recovery, micromeritc properties, incorporation efficiency. The factors of effect on the formation and the release rate of microspheres were also investigated.

RESULTSThe recovery of microspheres (280-900 microns) was more than 70% and the bulk density was around 0.7 kg.L-1. The incorporation efficiency always exceeded 95%. The formation of microspheres was mainly affected by the amount of bridging liquid and the emulsifying agents in poor solvent. The release rate of nitrendipine from the microspheres could be controlled as desired by adjusting the ratio of talc to Eudragit RS PO in the formulation.

CONCLUSIONThe presented method was suitable for preparing sustained-release microspheres of a water insoluble drug.

Delayed-Action Preparations ; Drug Carriers ; Microspheres ; Nitrendipine ; administration & dosage ; Particle Size ; Technology, Pharmaceutical ; methods

Hypertension is the most important potentially reversible risk factor for stroke in all age groups; high blood pressure (BP) is also associated with increased risk of recurrent stroke in patients who have already had an ischemic or hemorrhagic event. Twenty-four hour ambulatory BP monitoring (ABPM) has become an important tool for improving the diagnosis and management of hypertension, and is increasingly used to assess patients with hypertension. Nevertheless, although ABPM devices are increasingly used for assessment of hypertension, their value in the chronic management of hypertension in patients with stroke has not been systematically studied. In fact, among large-scale randomized trials for secondary stroke prevention, only the Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention trial included 24-hour ABPM. ABPM has demonstrated chronic disruption of the circadian rhythm of BP after acute phase of stroke and has shown higher sensitivity compared to office BP in evaluating the effectiveness of antihypertensive treatment among stroke survivors. High 24-hour BP is an independent predictor for cerebrovascular events, brain microbleeds, and subsequent development of dementia. Nevertheless, although stroke care guidelines endorse the importance of hypertension management, the specific role of ABPM among stroke survivors after the acute phase of disease has not been established. Further studies are needed to clarify whether routine application of ABPM among these patients should be recommended.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory* ; Brain ; Circadian Rhythm ; Dementia ; Diagnosis ; Humans ; Hypertension* ; Mortality ; Nitrendipine ; Risk Factors ; Secondary Prevention ; Stroke* ; Survivors

Hypertension is the most important potentially reversible risk factor for stroke in all age groups; high blood pressure (BP) is also associated with increased risk of recurrent stroke in patients who have already had an ischemic or hemorrhagic event. Twenty-four hour ambulatory BP monitoring (ABPM) has become an important tool for improving the diagnosis and management of hypertension, and is increasingly used to assess patients with hypertension. Nevertheless, although ABPM devices are increasingly used for assessment of hypertension, their value in the chronic management of hypertension in patients with stroke has not been systematically studied. In fact, among large-scale randomized trials for secondary stroke prevention, only the Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention trial included 24-hour ABPM. ABPM has demonstrated chronic disruption of the circadian rhythm of BP after acute phase of stroke and has shown higher sensitivity compared to office BP in evaluating the effectiveness of antihypertensive treatment among stroke survivors. High 24-hour BP is an independent predictor for cerebrovascular events, brain microbleeds, and subsequent development of dementia. Nevertheless, although stroke care guidelines endorse the importance of hypertension management, the specific role of ABPM among stroke survivors after the acute phase of disease has not been established. Further studies are needed to clarify whether routine application of ABPM among these patients should be recommended.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory* ; Brain ; Circadian Rhythm ; Dementia ; Diagnosis ; Humans ; Hypertension* ; Mortality ; Nitrendipine ; Risk Factors ; Secondary Prevention ; Stroke* ; Survivors

AIMTo evaluate the in vitro/in vivo correlation for three kinds of self-designed sustained-release nitrendipine formulations using deconvolution method.

METHODSThe characteristics of in vivo release were calculated by deconvolution method using the data of plasma concentration of three kinds of self-designed sustained-release nitrendipine formulations in healthy dogs, in which the in vivo results of nitrendipine solution after oral administrated to dogs were used as weight function. It was the compared with characteristics of in vitro release to assess the in vitro/in vivo correlations.

RESULTSThe good correlations of in vitro/in vivo were shown in three kinds of self-designed sustained-release nitrendipine formulations using deconvolution method.

CONCLUSIONThe deconvolution method exhibited advantage in evaluation of in vitro/in vivo correlation for self-designed sustained-release nitrendipine formulations.

Administration, Oral ; Animals ; Delayed-Action Preparations ; Dogs ; Methylcellulose ; analogs & derivatives ; Microspheres ; Nitrendipine ; administration & dosage ; blood ; pharmacokinetics ; Powders ; Silicone Gels ; Technology, Pharmaceutical ; methods

BACKGROUND: It has been shown that cerebral ischemia alters brain acetylcholine (Ach) metabolism. In an attempt to elucidate the mechanisms for ischemia-induced release of Ach in vitro, the effects of drugs which can influence the cholinergic neurotransmission on the ischemia-induced release of [3H]Ach from cerebral cortical slices of the rat were examined. METHODS: The cortices of decapitated rats were chopped and dispersed in artificial CSF. Then, the tissue suspensions were incubated with [3H]choline. The tissues were transferred and incubated in washing, hypoglycemic (deprivation of glucose), ischemic (deprivation of oxygen and glucose) and extracting plates sequently. Ischemia-induced release of [3H]Ach was expressed as percentage of the total [3H]Ach present in the slices. RESULTS: Ischemia induced significant release (about 9.3% of total tissue content) of [3H]Ach from cerebral cortical slices in vitro. This [3H]Ach release was significantly attenuated by tetrodotoxin, a voltage-sensitive Na+-channel blocker, and Mg2+, a physiological N-methyl-D-aspartate (NMDA) receptor blocker. Vesamicol (1 M), a blocker of vesicular transport of Ach, MK-801 and ketamine, NMDA receptor antagonists, 6,7-nitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), kainate/AMPA receptor antagonists, and 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX), a AMPA receptor blocker attenuated the [3H]Ach. Nitrendipine, nimodipine, inhibitor of L-type Ca2+ channels, and -conotoxin GVIA, an inhibitor of N-type Ca2+ channels, significantly attenuated the ischemia-induced release of [3H]Ach. Omission of Ca2+ from incubation media attenuated the ischemia-induced [3H]Ach release. Inhibitors of intracellular Ca2+ release, dantrolene and TMB-8, and a cell-permeable calcium chelator, 1,2-bis (2-aminophenoxy)-ethane-N, N, N+, N+-tetraacetic acid tetrakis (acetoxymethyl) ester (BAPTA-AM), inhibited the ischemia-evoked [3H]Ach release. CONCLUSION: These results suggest that the ischemia can induce Ach rele.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Acetylcholine ; Animals ; Brain ; Brain Ischemia ; Calcium ; Dantrolene ; Dizocilpine Maleate ; Ischemia ; Ketamine ; Metabolism ; N-Methylaspartate ; Nimodipine ; Nitrendipine ; Oxygen ; Rats* ; Receptors, AMPA ; Suspensions ; Synaptic Transmission ; Tetrodotoxin

The ryanodine receptor, a Ca2+ release channel of the sarcoplasmic reticulum (SR), is responsible for the rapid release of Ca2+ that activates cardiac muscle contraction. In the excitation-contraction coupling cascade, activation of SR Ca2+ release channel is initiated by the activity of sarcolemmal Ca2+ channels, the dihydropyridine receptors. Previous study showed that the relaxation defect of diabetic heart was due to the changes of the expressional levels of SR Ca2+ ATPase and phospholamban. In the diabetic heart contractile abnormalities were also observed, and one of the mechanisms for these changes could include alterations in the expression and/or activity levels of various Ca2+ regulatory proteins involving cardiac contraction. In the present study, underlying mechanisms for the functional derangement of the diabetic cardiomyopathy were investigated with respect to ryanodine receptor, and dihydropyridine receptor at the transcriptional and translational levels. Quantitative changes of ryanodine receptors and the dihydropyridine receptors, and the functional consequences of those changes in diabetic heart were investigated. The levels of protein and mRNA of the ryanodine receptor in diabetic rats were comparable to these of the control. However, the binding capacity of ryanodine was significantly decreased in diabetic rat hearts. Furthermore, the reduction in the binding capacity of ryanodine receptor was completely restored by insulin. This result suggests that there were no transcriptional and translational changes but functional changes, such as conformational changes of the Ca2+ release channel, which might be regulated by insulin. The protein level of the dihydropyridine receptor and the binding capacity of nitrendipine in the sarcolemmal membranes of diabetic rats were not different as compared to these of the control. In conclusion, in diabetic hearts, Ca2+ release processes are impaired, which are likely to lead to functional derangement of contraction of heart. This dysregulation of intracellular Ca2+ concentration could explain for clinical findings of diabetic cardiomyopathy and provide the scientific basis for more effective treatments of diabetic patients. In view of these results, insulin may be involved in the control of intracellular Ca2+ in the cardiomyocyte via unknown mechanism, which needs further study.
Animals ; Calcium Channels, L-Type ; Calcium-Transporting ATPases ; Diabetic Cardiomyopathies* ; Heart ; Humans ; Insulin ; Membranes ; Myocardium ; Myocytes, Cardiac ; Nitrendipine ; Rats* ; Relaxation ; RNA, Messenger ; Ryanodine Receptor Calcium Release Channel* ; Ryanodine* ; Sarcoplasmic Reticulum*

OBJECTIVETo study the toxicity on skin and penetration effect of volatile oil from tender branchers of Camellia oleifera on nitrendipine, baicalin, nimesulide for percutaneous obsorption.

METHODAcute skin toxicity, irritation and allergy on rats were tested, and mouse skin in vitro was applied for studying the effects of different concentrations of volatile oil in nitrendipine, baicalin, nimesulide on drug permeation.

RESULTDifferent dosage volatile oil had no acute toxicity, irritation or hypersensitive effects. Compared to azone, more powerful enhancement effects of volatile oil at different concentration on nitrendipine, baicalin, nimesulide were very obvious.

CONCLUSIONThis paper firstly reported the results of experiment about the toxicity to skin and penetr-ation effect of volatile oil from tender branches of C. oleifera.

Administration, Cutaneous ; Animals ; Camellia ; chemistry ; Female ; Flavonoids ; administration & dosage ; pharmacokinetics ; In Vitro Techniques ; Male ; Mice ; Nitrendipine ; administration & dosage ; pharmacokinetics ; Oils, Volatile ; isolation & purification ; pharmacology ; toxicity ; Permeability ; drug effects ; Plant Oils ; isolation & purification ; pharmacology ; toxicity ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; Skin Absorption ; drug effects ; Sulfonamides ; administration & dosage ; pharmacokinetics

OBJECTIVETo explore the modulatory effect of niflumic acid and blocker of calcium channel on the desensitization of gamma aminobutyric acid (GABA)-activated currents in dorsal root ganglion(DRG) neurons from rat.

METHODSThe whole-cell patch-clamp technique was used to observe the modulatory effect of niflumic acid and blocker of calcium channel on the desensitization of GABA-activated currents in neurons freshly dissociated from rat DRG neurons.

RESULTSApplication of GABA (0.1-1 000 micromol/L) could induce concentration-dependent inward currents in some cells (212/223, 95.11%). GABA-(100 micromol/L) activated currents was (1.32 +/- 0.74) nA (n = 84). However, pre-application of niflumic acid (1-100 micromol/L) and nitrendipine (specific blocker of L-calcium channel)(0.1-30 micromol/L) could inhibit the GABA-activated inward current which was identified to be GABAA receptor-mediated current. The inhibitory effects of niflumic acid and nitrendipine were concentration-dependent. The suppression rate of 10 micromol/L niflumic acid and nitrendipine to GABA-activated currents were (31.60% +/- 4.87%) (n = 19) and (43.60% < or = 5.10%) (n = 5), respectively. The desensitization of GABA-activated currents had double exponential characteristic. Tau value was (14.68 +/- 5.11) s (n = 6) and (175.8 +/- 42.67) s (n = 6, r = 0.9647), respectively. Pre-application of niflumic acid (100 micromol/L) and nickel chloride (nonspecific blocker of L-calcium channel) (100 micromol/L) altered tau value of the desensitization of GABA-activated currents, tau value reduced for (4.64 +/- 2.21) s (n = 3), (43.70 +/- 14.34) s ( n = 3, r = 0.9548) and (4.64 +/- 2.21) s (n = 3), (43.70 +/- 14.34) s (n = 3, r = 0.9721).

CONCLUSIONPre-application of niflumic acid exerts a more strong inhibitory effect on the peak value of GABA-activated current, which possibly is through blocking the calcium-activated chloride ion channel to accelerate the desensitization of GABA-activated currents.

Animals ; Animals, Newborn ; Calcium Channel Blockers ; pharmacology ; Calcium Channels, L-Type ; drug effects ; Ganglia, Spinal ; drug effects ; physiology ; Membrane Potentials ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Niflumic Acid ; pharmacology ; Nitrendipine ; pharmacology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; pharmacology