ANTIHYPERTENSIVE EFFECTS OF MESULERGINE: FURTHER EVIDENCE FOR A PERIPHERAL SITE OF ACTION OF DOPAMINE AGONISTS

The cardiovascular effects of mesulergine were studied in anesthetized dogs. Intravenous (IV) administration (0.3 mg/kg) significantly decreased blood pressure in neurogenic hypertensive dogs without any change in heart rate. This effect was completely antagonized by IV administration of domperidone (0.5 mg/kg). Intracisternal administration of mesulergine (0.03, 0.3 and 3 mg/kg) did not produce any change in blood pressure. However, with the highest dose we observed a significant rise in heart rate during the first 2 min (which was probably nonspecific). These results suggest that mesulergine lowers blood pressure in sinoaortic-denervated dogs by means of a peripheral mechanism probably involving DA2 receptors. The findings confirm the potential interest of dopamine-receptor agonists as future antihypertensive agents.     

Metoclopramide,domperidone and dopamine in man: actions and interactions

Summary The effects of oral doses of the dopamine antagonist antiemetics metoclopramide and domperidone on baseline and dopamine stimulated renal function and systemic haemodynamics were assessed in a placebo controlled crossover study in 9 healthy volunteers.Metoclopramide did not change baseline ERPF, GFR or FF over 2 h post dosing but it significantly reduced baseline U_NaV, U_KV, urine flow, urinary dopamine excretion, supine and erect diastolic blood pressure and supine systolic blood pressure. Domperidone and placebo did not cause these effects.Metoclopramide caused a marked rise and domperidone a small fall in plasma aldosterone concentration (PAC) but placebo was without effect. Neither antiemetic altered plasma renin activity (PRA) but a small fall occurred with placebo.Two hours after pretreatment with placebo dopamine (2 g/kg/min) increased effective renal plasma flow (ERPF), glomerular filtration rate (GFR), sodium excretion rate (U_NaV), urine flow rate, urinary dopamine excretion rate, supine systolic blood pressure and supine and erect pulse rate and decreased the potassium excretion rate (U_KV), filtration fraction (FF) and supine diastolic blood pressure.Metoclopramide pretreatment, did not attenuate the dopamine induced rise in ERPF, GFR, urine flow, urinary dopamine excretion or supine systolic blood pressure but it did attenuate the rise in pulse rate, the fall in diastolic pressure, and the antikaliuretic effect of dopamine leading to a net kaliuresis when compared to placebo. Domperidone was similar to placebo.Neither metoclopramide nor domperidone given orally caused clinically important antagonism of the renal haemodynamic effects of dopamine. However the effects of metoclopramide on blood pressure and electrolyte excretion may have clinical importance.Metoclopramide has significant pharmacodynamic effects which are probably not due to DA₂ antagonism but may be mediated by DA₁ antagonism or be non-specific.Abbreviations DA dopamine - ERPF effective renal plasma flow - FF filtration fraction - GFR glomerular filtration rate - PAC plasma aldosterone concentration - PRA plasma renin activity - UV urine flow rate - U_NaV urinary sodium excretion rate (natriuresis) - U_KV urinary potassium excretion rate (kaliuresis) - HPLC high performance liquid chromatography.     

伊托必利治疗功能性消化不良的随机双盲对照试验104例

目的:观察国产伊托必利片治疗功能性消化不良的疗效和药物安全性。方法:将209例功能性消化不良病人,采用随机双盲、阳性药物对照试验方法,随机分为2组,伊托必利(受试)组给伊托必利50mg,餐前口服,每日3次;多潘立酮(对照)组给多潘立酮10mg,餐前口服,每日3次。疗程均为2或4wk。结果:伊托必利组治疗功能性消化不良总有效率为89%,与对照组多潘立酮(89%)相比无差异(P>0.05);明显改善病人消化不良临床症状和体征,显著改善胃排空功能(P<0.01),与对照组相比无差异。伊托必利组不良反应发生率为4%,与多潘立酮组(5.9%)比较无统计学差异。结论:伊托必利治疗功能性消化不良是安全、有效。     

胃排空迟缓症的超声动力学检测

目的:为找到一种简便的研究胃排空迟缓症的方法,应用B超进行了胃动力学检测。方法:应用B超测定了30例正常人和65例非溃疡性消化不良(NUD)患者液体、半流质和固体食物的胃排空时间。观察了胃排空迟缓症三种试餐排空的差别、症状特点及胃动力药的治疗效果。结果:与正常人比,65例NUD患者中13例显示固体食物胃排空迟缓,其中11例(84.6％)同时有半流质食物排空迟缓,只有1例(7.7％)同时有液体食物排空迟缓。胃排空迟缓症患者固体和半流质食物排空迟缓多见。胃排空迟缓症患者的症状以腹胀、早饱、食欲下降为主,而胃排空正常的NUD患者的症状以腹痛为主。吗丁啉可迅速改善胃排空迟缓症的症状,服药后固体食物胃排空时间(4.00±0.50h)较服药前(5.22±0.75h)显著缩短(P<0.01)。结论:表明B超测定胃排空时间是一种完全在生理条件下进行的、准确、安全、适用的方法。     

复方阿嗪米特肠溶片联合多潘立酮片治疗缺铁性贫血治疗后腹部不适的疗效观察

目的观察复方阿嗪米特肠溶片联合多潘立酮片治疗缺铁性贫血治疗后腹部不适的效果及安全性。方法经血常规和骨髓化验确诊的缺铁性贫血患者119例,男22例,女97例,随机分为复方阿嗪米特肠溶片+多潘立酮片组(治疗组,84例)和多潘立酮片组(对照组,35例)进行治疗,复方阿嗪米特肠溶片2片/次,3次·d-1,餐后;多潘立酮片1片/次,3次·d-1,餐前0.5 h,疗程均为4周。观察服药前后纳差、餐后饱胀、早饱、上腹痛、上腹烧灼感、嗳气、恶心呕吐、便秘及难以描述的上腹部不适感等症状的积分和药物不良反应情况。结果治疗4周后,治疗组显效率和总有效率优于对照组,差异有统计学意义(P<0.01);治疗组复发率明显低于对照组,差异有统计学意义(P<0.01);2组均未观察到严重的药物相关性不良反应。结论复方阿嗪米特肠溶片联合多潘立酮片治疗缺铁性贫血治疗后腹部不适的疗效满意,复发率低,且安全有效。     

Pharmacokinetics of trimethylamine in rats,including the effects of a synthetic diet

1. The pharmacokinetic profile of trimethylamine (TMA) was examined in the male Wistar rat and the effects of a synthetic diet on TMA pharmacokinetics were also evaluated. 2. The concentrations of TMA and its N -oxide in blood were analysed by a sensitive headspace gas chromatographic assay. 3. The pharmacokinetics of TMA were essentially linear for intravenous (i.v.) bolus doses of 10-40?mg kg -1. Over the range of administered i.v. doses, the concentrations of TMA in blood declined approximately monoexponentially with half-lives of 2.03-2.48?h. The V d of TMA ranged from 3.2 to 4.39?l kg -1 and clearance ranged from 18.78 to 23.92ml?min -1 kg -1. The peak concentration of TMA in blood occurred at 1?h after oral administration of a 20?mg kg -1 dose and the bioavailability for the oral dose averaged 81%. 4. Peak concentrations of trimethylamine N -oxide (TMAO) in blood were attained at 0.75 and 1?h after i.v and oral administration of TMA (20mg kg -1), respectively. 5. Feeding the male Wistar rat with a synthetic diet resulted in a twofold decrease in the clearance of TMA. Furthermore, the concentration of TMAO in blood after i.v. administration of TMA peaked at 1.25?h in rat placed on the synthetic diet as opposed to 0.75?h in rat placed on normal laboratory rat chow. The altered pharmacokinetic profile of TMA and its N -oxide suggest a diminished drug-elimination capacity in rat placed on the synthetic diet. 6. Dietary modulation of flavin-containing monooxygenase (FMO) activity may explain the effects of diet on the pharmacokinetics of TMA and its N -oxide.     

多潘立酮口腔崩解片在健康人体的生物等效性

目的观察多潘立酮口腔崩解片(胃动力药)在健康人体的生物等效性。方法22名健康受试者随机交叉单剂口服多潘立酮口腔崩解片剂及多潘立酮片剂后,用HPLC法测定多潘立酮血药浓度。结果2种制剂的Cmax分别为(40.43±12.89),(42.31±20.32)μg·mL-1;tmax分别为(0.84±0.29),(0.91±0.48)h;t1/2(ke)分别为(11.23±5.06),(10.13±4.02)h;AUC0-tn分别为(187.61±81.20),(189.07±97.69)μg·h·mL-1;AUC0-∞分别为(220.18±106.93)和(215.57±102.13)μg·h·mL-1;F0-tn、F0-∞分别为(102.61±16.41)%和(101.96±16.06)%。结论试验制剂和参比制剂具有生物等效性。