Comparison of the effects of dilevalol and propranolol on systemic and regional haemodynamics in healthy volunteers at rest and during exercise

The effects of single oral doses of dilevalol 400 mg and propranolol 80 mg on systemic and regional haemodynamics at rest and after sub-maximal exercise, were compared, in a placebo-controlled, randomised, double-blind, crossover study in 6 healthy male volunteers.At rest, as compared to placebo, neither dilevalol nor propranolol significantly affected arterial pressure and heart rate but, whereas propranolol decreased cardiac output (–27% at 2 h) and tended to increase total peripheral resistance, dilevalol tended to increase cardiac output and decreased total peripheral resistance (–7% at 2 h). Neither dilevalol nor propranolol affected brachial artery diameter. Propranolol tended to decrease brachial artery flow (–20% at 2 h) and to increase brachial vascular resistance (+25% at 2 h), but dilevalol did not and the brachial irrigation ratios did not change. Neither of the drugs affected carotid haemodynamics or plasma atrial natriuretic factor. Both drugs tended to decrease plasma renin activity, and dilevalol (+82% at 2 h) increased norepinephrine more than propranolol (+19% at 2 h).After exercise, dilevalol and propranolol produced similar falls in the induced increases in arterial pressure, heart rate and cardiac output, and had the same effects on regional haemodynamics, plasma renin activity and atrial natriuretic factor. Finally, dilevalol greatly increased plasma norepinephrine.We conclude that the ₂-adrenoceptor agonist activity of dilevalol was clearly expressed at rest, thus inducing vasodilation and counteracting the -adrenoceptor blockade-induced negative chronotropic and inotropic effects. However, during sub-maximal exercise, only the -adrenoceptor antagonist activity of dilevalol was apparent.     

Effects of a finnish sauna on the pharmacokinetics and haemodynamic actions of propranolol and captopril in healthy volunteers

The effects of a Finnish sauna on propranolol pharmacokinetics and on the pharmacodynamics of propranolol and captopril were studied in healthy, young volunteers (2 males, 6 females) in a double-blind, cross-over trial. The subjects received single oral doses of placebo. propranolol (40 mg) or captopril (12.5 mg) in sauna and control sessions at a one-week interval. The sauna sessions consisted of three repetitive 10-min stays in a sauna (85–100°C, relative humidity 25–35%) separated by two 5-min rest periods in a cool room. Sauna bathing started 35, 50 and 65 min after ingestion of the drugs. Venous blood for plasma propranolol measurement were collected before and 15, 30, 45, 60, 75, 90 min and 2, 3, 4, 5, 7 and 24 h after drug intake. The sauna significantly increased the maximum concentration (C_max 41 vs. 28 ng·ml^–1) of propranolol and the mean plasma propranolol concentration 60 and 90 min, and 2 and 3 h after drug administration. It also significantly increased the AUC_0–5h (119 vs 71 g·h·l_-1) of propranolol from 0 to 5 hours t_max, t_1/2 and AUC_0–24h of propranolol did not differ between the control and sauna sessions. The higher propranolol levels during and after the cessation of sauna bathing did not lead to significant changes in blood pressure or heart rate compared to the control period. Captopril had no major effects on these parameters during the post-sauna phase. The results suggest that a sauna may increase the plasma propranolol concentration, but that did not notably affect the blood pressure or heart rate in healthy, young volunteers during the post-sauna phase.     

The effect of l-dopa and propranolol on human CSF cyclic nucleotides

Human CSF cyclic AMP and cyclic GMP have been measured as possible indicators of activity of central neurotransmitter-sensitive adenylate or guanylate cyclase. In an attempt to help to identify the specific neurotransmitter systems of origin of human CSF cyclic AMP and GMP, we studied Parkinson patients with and without l-dopa therapy and schizophrenic patients before and after propranolol therapy. No effect of l-dopa or propranolol was found on CSF cyclic nucleotides. However, Parkinson patients had a 40–50% reduction of CSF cyclic AMP and a 80–90% reduction of CSF cyclic GMP compared with the schizophrenic patients. Implications of this finding are discussed.     

Decrease of some metabolic and physiologic effects of diazoxide by propranolol in rat

Summary Diazoxide significantly decreased the blood pressure and relaxed the uterine muscle in anaesthetized normotensive rats. A marked elevation of blood glucose followed the intravenous injection of diazoxide. The hyperglycemic and the uterine relaxing response could be significantly decreased by injection of propranolol prior to diazoxide. The hypotensive effect was not diminished by propranolol, however. In liver and uterus the content of cAMP was increased following diazoxide treatment in vivo. The rise in cAMP could be completely inhibited by propranolol, indicating a -receptor stimulation being the cause of the cAMP elevation.     

Evidence for involvement of 5-HT1C and 5-HT2 receptors in the food intake suppressant effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)

Administration of various doses of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) to rats produced dose-related decreases in 1-h food intake in the food-deprived paradigm. Pretreatment with spiperone (5-HT_1A/5-HT₂/D₂ antagonist), propranolol or CGP361A (-adrenoceptor antagonists that also have binding affinities for 5-HT_1A and 5-HT_1B sites) and MDL-72222 (5-HT₃ antagonist) did not attenuate DOI-induced suppression of food intake. In contrast, pretreatment with metergoline (5-HT₁/5-HT₂ antagonist) completely blocked whereas mesulergine, mianserin and ritanserin (5-HT_1C/5-HT₂ antagonists) partially blocked DOI's effect on food intake. On the other hand, pretreatment with MDL-72222 but not with m-chlorophenylpiperazine (m-CPP) significantly potentiated DOI-induced suppression of food intake. Furthermore, the food intake suppressant effects of various doses of DOI were found to be similar in the Fawn-Hooded (FH) rat strain as compared to the Wistar rat strain. These findings suggest that DOI-induced suppression of food intake is mediated by stimulation of both 5-HT_1C and 5-HT₂ receptors.     

Acute changes in forearm haemodynamics produced by cigarette smoking in healthy normotensive non-smokers are not influenced by propranolol or pindolol

Summary The aim of the present study was to examine the effect of cigarette smoking in healthy non-smokers on blood pressure and forearm haemodynamics after acute oral administration of non-selective -adrenoceptor blockers with and without intrinsic sympathomimetic activity, viz. pindolol 15 mg and propranolol 80 mg. A preliminary study was done to compare cigarette smoking and sham smoking to evaluate the time-course of the haemodynamic effects of cigarette smoking. The second experiment was then carried out in the same six volunteers, according to a double-blind randomized placebo-controlled crossover design, to evaluate the possible effect of pre-treatment with -adrenoceptor blockers on blood pressure, heart rate and forearm haemodynamics (forearm blood flow, brachial artery diameter and brachio-radial pulse-wave velocity) measured at baseline, during smoking and every five minutes up to 1 h afterwards.No major difference from placebo in blood pressure or forearm haemodynamics was found and pre-treatment with beta-blockers did not prevent the acute vascular effects of cigarette smoking.     

Noradrenergic and dopaminergic interactions in escape behavior: Analysis of uncontrollable stress effects

The effects of norepinephrine receptor blockade on the deficits of escape behavior induced by haloperidol and by inescapable shock were evaluated. Phenoxybenzamine, the -norepinephrine receptor blocker, was found to enhance escape behavior and to eliminate the disruptive effects of both inescapable shock and haloperidol. In contrast, the -norepinephrine receptor antagonist, propranolol, was without effect on behavior under any of these conditions, while the dopamine--hydroxylase inhibitor, FLA-63, disrupted performance. Like phenoxybenzamine, the norepinephrine receptor stimulant, clonidine, was found to eliminate the behavioral disruption produced by haloperidol. These somewhat paradoxical findings were discussed in terms of the contribution of DA-NE interactions in determining behavioral change in aversive paradigms.     

Circling behavior following systemic d-amphetamine administration: Potential noradrenergic and dopaminergic involvement

Systemic treatment with d-amphetamine produced a dose-dependent increase in the circling behavior of normal mice. Treatment with both -methyl-p-tyrosine (-MpT) and FLA-63 antagonized the amphetamine-induced circling behavior. Similarly, blockade of B-adrenergic receptors by propranolol and dopamine receptors by haloperidol reversed the circling response elicited by amphetamine. In contrast to -MpT and haloperidol, however, neither FLA-63 nor propranolol attenuated the locomotor excitation engendered by amphetamine. Following repeated d-amphetamine injections the circling ordinarily induced by a single injection was abolished, whereas the locomotor effects of amphetamine remained unaltered. These findings are consistent with earlier work suggesting that tolerance may occur in those behaviors that involve a noradrenergic component.     

5-单硝酸异山梨醇酯联合普萘洛尔治疗肝硬化门静脉高压

目的观察5-单硝酸异山梨醇酯联合普萘洛尔对肝硬化门静脉血流动力学的影响。方法22例肝硬化患者口服5-单硝酸异山梨醇酯20mg,2次/d,普萘洛尔10～20mg,3次/d,共8周。于治疗前及治疗后4周、8周分别检测门静脉血流动力学参数。结果联合治疗后4周、8周均可以显著降低肝硬化患者门静脉内径、血流速度及血流量(P<0.01)。于治疗8周后,脾静脉内径也较治疗前缩小(P<0.05)。结论5-单硝酸异山梨醇酯联合普萘洛尔可以显著降低门静脉血流量。     

高效液相色谱法测定盐酸普萘洛尔片含量

目的:采用高效液相色谱法测定盐酸普萘洛尔片的含量.方法:Diamonsil C18柱(4.6 mm×150 mm,5μm)为分析柱,流动相为甲醇-0.02 mol·L-1磷酸二氢钾溶液(50:50),流速0.9 ml·min-1,检测波长290nm.结果:盐酸普萘洛尔在50.7～405.9μg·ml-1范围内呈良好的线性关系,r=0.999 9,平均回收率为99.2%,RSD=0.92%(n=9).结论:本方法简单、快速、结果可靠.