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1.
Summary The pharmacokinetics of ketanserin and its main metabolite ketanserin-ol, and the antihypertensive effects of intravenous, single oral and chronic oral (40 mg once daily) administration of ketanserin, have been investigated in a single blind study of 10 patients with uncomplicated mild hypertension. Ketanserin had a terminal half-life of 29.2 h, a plasma clearance of 518 ml/min and a volume of distribution of 18.0 l/kg. Chronic oral intake of 40 mg ketanserin (tablet formulation) gave a peak concentration of unchanged ketanserin of 88 ng/ml after 1.1 h. Its absolute bioavailability was 48%.During chronic therapy the maximal concentration of ketanserin-ol was 208 ng/ml and its half-life of elimination was 35.0 h. As this metabolite can be oxidized back to ketanserin, it contributes to the prolonged half-life of unchanged ketanserin seen during chronic therapy.The blood pressure was reduced by approximately 15% by oral ketanserin. The maximal reduction in blood pressure coincided with the peak concentration of unchanged ketanserin. During chronic therapy with 40 mg once daily blood pressure was reduced over 24 h. The heart rate was slightly reduced and the cardiovascular responses and the plasma noradrenaline concentrations during isometric exercise were only slightly influenced by ketanserin therapy.Thus, unchanged ketanserin has a relatively long half-life during chronic oral therapy and its pharmacokinetics in middle-aged hypertensive patients is similar to that in normal young volunteers. 相似文献
2.
Ketanserin降低清醒自发性高血压大鼠血压波动性的机理初探 总被引:2,自引:0,他引:2
应用计算机化清醒大鼠血流动力学测定技术,观察5-HT2受体阻滞剂Ritanserin(Rit)和α1受体阻滞剂哌唑嗪对清醒自发性高血压大鼠(SHR)的血压、血压波动性(BPV)和动脉压力感受性反射血压控制部分(ABR-BP)的效应,旨在初步探讨兼具5-HT2受体和α1受体阻滞作用地新型抗高血压药Ketanserin降低BPV的机制。结果表明:Rit对SHR无降压作用,但侧脑室给药明显提高ABR-B 相似文献
3.
Angela J. Drake-Holland Mark I. M. Noble Sara Pugh Christopher Mills 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1988,2(2):239-243
Summary In this study any changes in action potential duration or Q-T interval due to acute doses of ketanserin were monitored. The effect of a bolus dose (10 or 20 mg) followed by an infusion (10 or 20 mg over 20 minutes) of ketanserin on the Q-T interval and action potential duration was studied in six patients undergoing routine cardiac catheterization. Action potential duration was measured with a silver-silver chloride electrode catheter while heart rate was kept constant by atrial pacing and reflex effects avoided by -adrenergic blockade. There were some prolongations of the action potential duration but they were not in excess of 40 msec and did not reach statistical significance (control 263±46.0 msec; bolus 269±52.1 msec; infusion 262±53.6 msec; nor were there any significant changes in Q-T interval. Thus acute intravenous doses of ketanserin, in the absence of hypokalaemia or other Q-T interval-prolonging drugs, have no consistent effect on Q-T interval or action potential duration; prolongation of the action potential, when it occurs, is small. 相似文献
4.
Sean T. McCarthy Gail L. McCarthy Sally M. John Susan E. Gould 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1990,4(1):115-117
Summary The results of the European Working Party for Hypertension in the Elderly Study showed that treatment of high blood pressure reduced the morbidity and mortality from strokes and myocardial infarction and reduced the incidence of heart failure in elderly patients. The largest number of hypertensive patients are elderly, and it is in this group of patients that the maximum benefit of treatment might be expected. The present study was designed to study in detail the efficacy and tolerability of ketanserin in an elderly population. Seventeen elderly (> 70 years) patients with a lying systolic blood pressure of 160 mmHg and/or a diastolic blood pressure of 90 mmHg were included in the study. For the 12 patients who completed the study, the mean blood pressure was significantly reduced on ketanserin compared with placebo (p<0.001) in the supine and erect positions. The mean net changes in blood pressure after 8 weeks were 21/17 mmHg and 23/16 mmHg erect. Heart rate was also significantly reduced (p<0.001) by a mean of 8 beats/min lying and 9 beats/min erect. Analysis of ambulatory 24-hour ECG tapes showed no significant effect of ketanserin on heart rhythms. Ketanserin therapy had no significant effect on routine hematology, plasma electrolytes, biochemistry, or urinalysis. Total exchangeable sodium and potassium and body weight were also unchanged. On ketanserin treatment, the overall quality of life score was significantly improved (p=0.002; analysis of variance on log transformed data) compared with the placebo phase. 相似文献
5.
Austin E. Doyle 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1990,4(1):13-18
Summary There is very suggestive evidence for a role of serotonin release from platelets in the mechanisms for platelet aggregation, arterial thrombosis, and arterial spasm. These effects are mediated via the 5HT2 receptor and are specifically antagonized by ketanserin. The recently published PACK study was a randomized controlled trial of the effects of ketanserin in patients with intermittent claudication. The purpose of the trial was to discover whether ketanserin treatment would reduce the incidence of atherosclerotic complications such as myocardial infarction or stroke. An unexpected adverse interaction between ketanserin and potassium-losing diuretics was observed, causing an excess of deaths in the group taking this combination of drugs. The intention-to-treat analysis showed no overall difference between ketanserin and placebo in terms of cardiovascular complications. Withdrawal of patients taking potassium-losing diuretics left insufficient numbers of patients in the study to answer the original question. However, the on-treatment analysis excluding those taking the combination suggested strongly, although did not prove, that ketanserin reduced thrombotic episodes by about 25%. It is concluded that the risks of interactions between many drugs and potassium-losing diuretics make the use of the latter undesirable. Further studies on ketanserin, possibly combined with thromboxane A2 inhibitors, seem highly desirable. 相似文献
6.
Rana Arslan Sule Aydin Dilara Nemutlu Samur Nurcan Bektas 《Saudi Pharmaceutical Journal》2018,26(4):541-545
It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT2A/2C, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300?mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300?mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5?mg/kg, i.p.), serotonin 5-HT2A/2C receptor antagonist ketanserin (1?mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1?mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5?mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300?mg/kg in tail-immersion test, at the doses of 150 and 300?mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies. 相似文献
7.
Absence of effects of ketanserin on renal prostacyclin and thromboxane A2 in essential hypertension 总被引:2,自引:0,他引:2
The anti-hypertensive effect of ketanserin, a new antagonist of 5-HT2-serotonergic receptors, was evaluated in 10 patients with uncomplicated essential hypertension. At the end of 2 weeks of placebo wash-out and following 2 and 4 weeks of treatment with ketanserin (20 mg twice daily), blood pressure and heart rate were measured both in the supine and standing position. In addition, before and at the end of treatment, plasma renin activity (PRA), plasma concentration of aldosterone and the nocturnal urinary excretion of 6-keto-PGF1 alpha and TXB2, the two metabolites that largely reflect the renal synthesis of prostacyclin and thromboxane, respectively, were determined. The study was carried out in a metabolic ward where the intake of sodium was adjusted to 100-120 mmol day-1. Ketanserin significantly reduced blood pressure both in the supine and standing position with no significant change of heart rate. The treatment did not produce any variation of PRA, aldosterone, urinary excretion of 6-keto-PGF1 alpha or TXB2. These results indicate that ketanserin reduces blood pressure without interfering with the renin-angiotensin-aldosterone system or the renal synthesis of prostacyclin and thromboxane. 相似文献
8.
Krishnarao Korlipara Susan E. Gould Natalie A. Taylor Anthony Chandler 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1990,4(1):127-131
Summary Beta-adrenoceptor antagonists (beta blockers) are a well-established first-line treatment for hypertension, but they have been associated with unwanted symptoms including cold extremities, lethargy, and nightmares. Ketanserin is a serotonin S2-receptor antagonist that has previously been shown to reduce blood pressure in hypertensive patients by reducing systemic vascular resistance. Hypertensive patients whose sitting diastolic blood pressure was 95 mmHg, despite at least 4 weeks therapy with an optimal dose of beta blocker, were selected for the study. The beta-blocker dose remained constant throughout the study, but patients were randomly allocated to receive ketanserin 20 mg twice daily, ketanserin 40 mg twice daily, or bendrofluazide 5 mg each morning plus placebo at night in addition to the beta-blocker therapy. One hundred and forty two patients completed the symptom questionnaire at randomization and after 12 weeks treatment. The treatment groups were well matched for age, sex, weight, and blood pressure. Blood pressure was reduced significantly by all treatments, and there were no between-group differences. Bendrofluazide adversely affected alertness (p<0.05) and concentration (p<0.01) whereas ketanserin had no significant effect and the ketanserin 20 mg twice daily group had better concentration than the bendrofluazide group (p<0.05). Ketanserin treatment reduced the incidence of nightmares (p<0.05 for 20 mg twice daily and 40 mg twice daily) and was an improvement over bendrofluazide treatment in this respect (p<0.05).Leg pain on walking (p<0.01) and at rest (p<0.05) was worse on bendrofluazide, whereas ketanserin treatment 20 mg twice daily improved incidence of leg pain on walking (p<0.05) and was an improvement over bendrofluazide treatment in this respect (p<0.05). Incidence of flushing was reduced by ketanserin 40 mg twice daily (p<0.01) more effectively than by bendrofluazide treatment (p<0.05).The present study indicated that serotonin antagonism by ketanserin can reduce the nightmares and sleep disturbance and reverse the deterioration in peripheral circulation that may accompany treatment with beta blockers.representing the KTN 165 study group 相似文献
9.
M. A. Nelson J. P. Coghlan D. A. Denton E. H. Mills C. D. Spence J. A. Whitworth B. A. Scoggins 《Clinical and experimental pharmacology & physiology》1984,11(6):597-604
Serotonin causes a dose related (0.1-20 micrograms/kg i.v.) increase in mean arterial blood pressure (MAP) and heart rate in conscious sheep. Ketanserin (0.1 mg/kg per h i.v.) causes a decrease in blood pressure, and an increase in heart rate. In the presence of ketanserin, serotonin induced increases in MAP are attenuated, or abolished, but the increases in heart rate are enhanced. Ketanserin (10 mg/kg per h i.v.) attenuates or abolishes the increase in blood pressure induced by the alpha-adrenoceptor agonist phenylephrine in conscious sheep. When administered in the presence of the alpha-adrenoceptor antagonist prazosin, ketanserin (0.1 mg/kg per h i.v.) fails to induce a further hypotensive response. These data suggest that in the conscious sheep ketanserin exhibits predominantly alpha-adrenoceptor antagonism. 相似文献
10.
Mark A. Nelson John P. Coghlan Derek A. Denton Judith A. Whitworth Bruce A. Scoggins 《Clinical and experimental pharmacology & physiology》1985,12(2):155-159
The role of serotonin (5HT) in the pathogenesis of ACTH-induced hypertension in sheep has been examined. The pressor responses to injections of 5HT (0.1-30 micrograms/kg) were similar in normotensive and hypertensive sheep. Prior treatment with the 5HT2 receptor antagonist ketanserin had no effect on the development of hypertension produced by ACTH administration. 相似文献