Adrenoceptor Blocking Drug Research Articles

Central α1-adrenergic and opiate systems in the control of the vagal tone in normotensive and spontaneously hypertensive rats

In anesthetized, normotensive β-blocked rats, the α 1-adrenoceptor blocking drug, AR-C 239 (300 μg/kg, i.v.) induced a bradycardic effect related to a central increase in the vagal tone. This bradycardia was inhibited by previous administration of naloxone, intravenously (1 mg/kg) or centrally (100 μg/kg, i.c.) injected. Naloxone, by itself did not change the heart rate. In brainstem membranes from normotensive rats, AR-C 239 did not influence the stereoselective binding of [ 3H]naloxone. In spontaneously hypertensive (SH) rats, naloxone peripherally or centrally administered did not influence the activation of the vagal tone induced by AR-C 239, in β-blocked animals. These results suggest the possible involvement of opiate release in the AR-C 239-induced vagal bradycardiac, in normotensive rats. They also afford new arguments for the existence of close interactions between central α-adrenergic and opiate systems in the cardiovascular regulation. The possible participation of κ-receptors in this effect is discussed. In addition, such an opiate mechanism triggered by central α 1-adrenoceptor blockade seems to be either absent or inactive in SH rats.

Pharmacokinetics and Concentration-Effect Relationships of Bevantolol (CI-775) in Normal Volunteers

The pharmacokinetic handling of the beta 1 selective adrenoceptor blocking drug, bevantolol, was studied in 12 healthy volunteers. After intravenous (i.v.) administration of 50 mg of the drug, there was a biexponential decline in plasma levels with a terminal elimination half life (t1/2) of 1.9 h (range 1.4-2.3 h) and a total apparent volume of distribution at equilibrium of 62 L. After oral administration of the same dose, the bioavailability averaged 57% (range 26-98%) and peak plasma levels varied over a threefold range. On average, less than 1% of the dose was eliminated unchanged in the urine, indicating that the clearance of the drug was accounted for almost entirely by metabolism. Plasma levels after oral dosing with food showed an average 75-min delay in achievement of peak plasma levels and an average 14% increase in the extent of bioavailability of the drug. A positive correlation (r = 0.79) existed between the logarithm of the plasma bevantolol level and the percentage of reduction in postexercise heart rate. A plasma drug level of approximately 200 ng/ml produced a 10% reduction in postexercise heart rate. Pharmacological studies using guinea pig atrial and tracheal tissue demonstrated that the beta-blocking potency and beta-selectivity of bevantolol were intermediate between those of metoprolol and atenolol.

Interaction between central α1- and α2-adrenoceptors on sympathetic tone in rats

The interaction between piperoxan and α 2-agonists on sympathetic tone was studied in rats. The sympatho-inhibitory effect of α 2-agonists (clonidine, guanfacine, B-HT 933) was assessed by recording heart rate in normotensive bilaterally-vagotomized rats. Clonidine (3 μg kg , i.c.v.) and B-HT 933 (100 μg kg , i.c.v.) induced a bradycardia which was fully reversed by piperoxan (30 μg kg , i.c.v.). However, in rats treated with guanfacine, piperoxan induced a partial recovery of the bradycardic effect. The injection of a small dose of the specific α 1-adrenoceptor blocking drug, AR-C 239 (10 μg kg , i.c.v.) which, by itself did not modify heart rate, completely inhibited the reversal effect of piperoxan in rats treated with clonidine, B-HT 933 or guanfacine. In rat brainstem membranes, B-HT 933 was found to bind to both α 1- and α 2-adrenoceptors and was as potent as clonidine in competing for α 1-sites bound by [ 3H]prazosin. On the other hand, in bilaterally vagotomized rats, piperoxan (30 μg kg , i.c.v.) induced an increase in blood pressure and heart rate which was inhibited by previous administration of AR-C 239 (10 μg kg , i.c.v.). These data suggest that, by inhibiting central α 2-adrenoceptors, piperoxan unmasks central α 1-adrenoceptor stimulation by endogenous catecholamines leading to an increase in the sympathetic tone, but a full recovery in heart rate could be observed only with the mixed α 1 and α 2-adrenoceptor agonists, clonidine and B-HT 933. In addition, these data further indicate that α 1-adrenoceptors are implicated in a tonic control of the sympathetic nerve activity in normotensive rats.

Bopindolol, Pindolol, and Atenolol in Patients with Chronic Obstructive Lung Disease

Twelve subjects with chronic obstructive lung disease and a partially reversible obstruction received increasing single doses (1, 2, 4, and 8 mg) of bopindolol, (a new beta 1- and beta 2-adrenoceptor blocking drug with intrinsic sympathomimetic activity), pindolol (7.5, 15, and 30 mg), and atenolol (50 and 100 mg). The actions of the drugs on lung function were assessed by whole-body plethysmography. Pindolol did not influence mean airway resistance (Raw). Bopindolol 1, 2, and 4 mg and atenolol 50 mg also exhibited a neutral effect on mean Raw. Atenolol 100 mg, however, induced a long-lasting increase in mean Raw, which was to a lesser extent the case with bopindolol 8 mg. Six of the 12 subjects tested reacted more sensibly. Increases in Raw of more than 10% were observed with bopindolol 2 mg (1 subject), bopindolol 4 mg (4 subjects), pindolol 30 mg (3 subjects), and atenolol 50 mg (3 subjects). This clearly points toward a potential risk of eventually developing severe bronchospasm with each type of beta-adrenoceptor blocking drug in patients with chronic obstructive lung disease and a reversible component of the bronchial obstruction. Nevertheless it is concluded that beta-adrenoceptor blocking drugs with intrinsic sympathomimetic activity such as bopindolol and pindolol compare favorably with cardioselective agents such as atenolol.

The Additional Properties of Beta Adrenoceptor Blocking Drugs

Beta adrenoceptor blocking drugs are all competitive inhibitors of the beta receptor although they may or may not possess, beta 1-(cardio)selectivity, intrinsic sympathomimetic activity (ISA) or partial agonist activity, alpha-blocking properties, while membrane stabilizing activity is now thought not to be important. Drugs with ISA give less of a reduction in resting and maximal exercising heart rate and consequently in cardiac output, than those without ISA. The possession of alpha-blocking activity also leads to less fall in cardiac output. Overall evidence suggests that peripheral resistance and peripheral blood flow is less reduced by ISA drugs. Post-beta blockade hypersensitivity which may be important in patients with ischemic heart disease if beta blocking drugs are suddenly stopped, is absent after beta-blocking drugs with ISA as they result in down regulation of beta receptors. Beta 1-selective drugs may result in less of a rise in blood pressure in response to isometric exercise, insulin hypoglycemia or smoking. There do not appear to be important differences in the effect on coronary flow. While presently available drugs can produce asthma in susceptible subjects there seems little doubt that beta 1 selective agents have less effect than other beta-blocking drugs, and give less inhibition of sympathomimetic bronchodilators. Nonselective, non ISA, beta-blocking drugs elevate triglycerides, cardioselective drugs possibly less so. Those with ISA may elevate HDL unlike those beta-blocking agents without this property. Beta adrenergic blocking drugs without ISA do not lower resting plasma noradrenaline, evidence suggests an increase; whereas those agents with marked ISA, suggests an increase; whereas those agents with marked ISA, e.g., pindolol, reduce it. Renin levels are lowered, but less so with ISA possessing agents. Some agents, e.g. atenolol, nadolol, sotalol, are hydrophilic, show poor brain penetration, are long-acting, are not liver metabolized, but are excreted by the kidneys unchanged. Others are lipophilic, e.g., metoprolol, propranolol, penetrate the brain, and are liver metabolized. Pindolol is metabolized about 50% by each route. Similarities between beta blocking drugs are dominant but differences are often clinically relevant.

A practice-integrated learning sequence (PILS)

A practice-related office-based CME program was implemented in which 790 primary care physicians treated 9160 patients with hypertension with a single beta adrenoceptor blocking drug. Fifteen percent of the patients did not meet enrollment criteria and twenty-eight percent of the patients were not managed according to the criteria established. Deficiencies were also found in history taking concerning drug side effects on follow-up visits. Physicians performance in these categories could not be predicted by self-assessment test scores or by physicians' self-evaluations of various aspects of their practice behaviors during the program. The Practice Integrated Learning Sequence (PILS) described in this report is a practicerelated, office-based educational process which can be useful in evaluating practice behavior and identifying areas for additional educational interventions.

Interference of labetalol metabolites in the determination of plasma catecholamines by HPLC with electrochemical detection

The alpha and beta adrenoceptor blocking drug labetalol is a potent antihypertensive agent in widespread clinical use. Its interference in the classical chemical estimations of urinary catecholamines and their metabolites has been the subject of several reports. Factitiously raised values have been noted in both the fluorimetric catecholamine assay, and the standard spectrophotometric procedure for total (free and conjugated) metadrenalines. To avoid such drug interference, modification of these methods is required in the estimation of catecholamines and their o-methylated metabolites. Alternatively, VMA estimations or plasma/urinary catecholamine measurements by radioenzymatic assay may be used in patients on labetalol. Although high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) methods for estimation of plasma catecholamines are now in widespread use, the interference of labetalol in this method has not been reported. We now report that significant direct interference of labetalol in the HPLC-ECD assay does indeed occur, and can yield spuriously raised adrenaline levels.

Permissive role of spinal α1-adrenoceptors in sudomotor efferents

The electrodermal potential (EDP) recorded in the forepaws of anaesthetized cats in response to stimulation of the cholinergic-sympathetic nervous system at different levels was taken as a measure for sudomotor activity. Electrical stimulation of the hypothalamus with square wave pulses (1 ms duration, 0.5–64 Hz, 2 s train length) at intervals of 1 min induced rate-dependent EDPs which were inhibited at all rates of stimulation by intravenous (i.v.) injection of doses < 40 μg/kg of the α 1-adrenoceptor blocking drug prazosin. However, prazosin (50–500 μg/kg i.v.) did not impair EDPs induced by preganglionic stimulation (0.5–64 Hz) or by injection of the nicotinic ganglion stimulant DMPP (50 μg/kg i.v.). Prazosin (50 μg/kg i.v.) inhibited EDPs induced by unilateral electrical stimulation (square wave pulses, 1 ms duration, 16 Hz, 2 s train length, 1 min intervals) of the spinal cord at C 1 in cats with an axotomy at the level of the medulla oblongata, thus indicating a spinal site of prazosin action and suggesting a permissive role of spinal catecholamines by activation of α 1-adrenoceptors. In spinal preparations pretreated with 250 μg/kg yohimbine i.v. to block inhibition by α 2-adrenoceptors of catecholamine reuptake, cocaine 2.5 mg/kg i.v. potentiated EDPs induced by spinal stimulation with 8 Hz. This effect could be antagonized by 50 μg/kg prazosin or 1000 μg/kg corynanthine i.v. In spinal preparations pretreatment with 5 mg/kg reserpine i.p. for depletion of catecholamines and 250 μg/kg yohimbine i.v., EDPs (16 Hz) were smaller than in undepleted preparations. Under these conditions injection of 100 μg/kg clonidine i.v. caused amplification of EDPs. This effect was antagonized by 50 μg/kg prazosin i.v. After i.v. pretreatment with 250 μg/kg yohimbine the i.v. injection of 2.5 mg/kg cocaine also potentiated EDPs which were induced by hypothalamic stimulation in intact cats. The results indicate that catecholaminergic neurons influence sudomotor activity by interaction with efferents of the cholinergic-sympathetic nervous system at the level of the spinal cord. Catecholamines seem to facilitate impulse transmission in non-catecholaminergic synapses by activation of α 1-adrenoceptors.

Tissue distribution of exaprolol in rat.

The disposition of the beta adrenoceptor blocking drug 1-(2-cyclohexylphenoxy)-3-isopropylamino-2-propanol, exaprolol, in organs of the rat has been studied. After i.v. administration of 3H-exaprolol a transient extremely high accumulation of the drug in lungs was observed with a peak of 7.7% of dose/g 30 min post-administration. The disposition pattern in heart, kidneys and liver may be characterized by a tissue to plasma ratio about ten. Lower exaprolol tissue levels were observed after oral administration. The tissue to plasma ratios showed an initial increase followed by constant levels. The distribution of exaprolol in organs of the rat is discussed in the light of the previously determined pharmacokinetic parameters.

Local anaesthetic effect of antiarrhythmic drugs and human sperm immobilization: mechanism and application of the interrelationship.

Sperm immobilizing activity of three class I antiarrhythmic drugs, quinidine, procainamide, mexiletine, one adrenoceptor blocking drug, labetalol and one calcium channel blocking drug, diltiazem was measured with a trans-membrane migration method. All these drugs immobilized human sperm. Local anaesthetic effect is the underlying mechanism for these drugs to inhibit sperm motility. Sperm immobilization could be a screening test for the local anaesthetic effect of antiarrhythmic drugs.

(R,R)-Labetalol hydrochloride: determination of the absolute configuration of the high-melting polymorph, C19H25N2O3+.Cl−

Mr=364.9 , orthorhombic, P21212~, a-- 31.04 (6), b= 19.21 (4), c= 6.57 (3)/k, V= 3888.2/k 3, Z=8, D x=1.25Mgm -3, 2(CuKa--)= 1.54051/k, /~= 1.796 mm -~, F(000)= 1552, T= 293 K. Final R = 0.075 for 3766 observed reflexions. The absolute configuration was determined as RR. There are two crystallographically independent molecules which have different conformations in the propyl chain. Both molecules adopt a conformation intermediate between 'perpendicular-trans' and 'planar-trans'. Introduction. The crystal studied was that of one of the four isomers present in the adrenoceptor-blocking drug labetalol hydrochloride (Brittain, Drew & Levy, 1982). The single enantiomer ((a) 2°'5°c-29.2 °(MeOH, 5.1 g dm-3)) (Hartley, Lunts, Collins, Hallett, Clifton & Wicks, 1982) was shown to be >99% isomerically pure as determined by GLC (Munro, Hunt, Rowe & Evans, 1978). This compound crystallizes in at least two polymorphs, and the one studied here (I) had a melting point of 468-469 K. The structure analysis has shown the absolute configuration to be RR.

The effect of d,l-4-hydroxypropranolol on the thyroxine to 3,5,3'-triiodothyronine conversion in rat renal and liver microsomes

The in vitro effect of D,L-4-hydroxypropranolol, a major pharmacological active metabolite of the beta adrenoceptor blocking drug D,L-propranolol, on the thyroxine (T4) to 3,5,3'-triiodothyronine (T3) conversion has been studied using rat renal and liver microsomal fractions. The results showed, that primarily the metabolite, but also the parent drug inhibits the T3-production in a dose dependent manner. The potency, expressed as the 50% inhibition of the T3-production, was reached using 65 +/- 12 (SD) microM D,L-4-OH-propranolol and 1000 +/- 22 (SD) microM D,L-propranolol, respectively in both tissues. The efficacy of 4-OH-propranolol corresponded to a maximal inhibition of 86 +/- 7% while it for D,L-propranolol corresponded to 58 +/- 6% (P less than 0.001). The beta adrenoceptor agonist isoprenaline itself did not effect the T4 to T3 conversion but considerably opposed the inhibitory effect of D,L-4-OH-propranolol but not of D,L-propranolol. The D-isomer form of propranolol, which is without beta receptor blocking activity inhibited the T3-production in the same degree as D,L-propranolol. Evaluation of the enzyme kinetic data suggested that 4-OH-propranolol caused a competitive inhibition of both T4 and DTT. It is concluded, that the metabolite D,L-4-OH-propranolol is a much more potent and efficacious inhibitor of the T4-5'-deiodination than D,L-propranolol.

Possible role of α1- and α2-adrenoceptors in the modulation of the sympathetic component of the baroreflex

In anaesthetized and bilaterally vagotomized dogs, reflex bradycardia elicited by intravenous injection of noradrenaline was facilitated by AR-C 239, a new α 1-adrenoceptor blocking drug and inhibited by the α 2-adrenoceptor antagonist, yohimbine. Both α-blocking drugs were administered into the vertebral artery. In another group of bilaterally vagotomized dogs, unilateral electrical stimulation of the carotid sinus nerve induced a frequency-dependent decrease in mean blood pressure solely mediated through the sympatho-inhibitory component of the baroreflex. Administration of the α 1-adrenoceptor blocking drugs, AR-C 239 and prazosin (5 μg/kg) into the vertebral artery decreased basal mean blood pressure and increased depressor responses to the carotid sinus nerve stimulation, whereas the intracisternal injection of phenylephrine (30 μg/kg), a preferential α 1-agonist, increased mean blood pressure but inhibited the hypotension resulting from electrical stimulation. In addition, the injection into the vertebral artery of yohimbine (100 μg/kg), an α 2-adrenoceptor blocking agent which caused no change in mean arterial pressure, inhibited the decrease in the sympathetic component. In conclusion, these results suggest the possible participation of the two types of α-adrenoceptors in the modulation of the sympathetic component of the baroreflex: α 1-adrenoceptor stimulation could inhibit, whereas α 2-adrenoceptor activation facilitates the reflex activity in the sympathetic fibres.

Central α1-adrenoceptors and cardiovascular control in normotensive and spontaneously hypertensive rats

Intracerebroventricular (i.c.v.) injection of AR-C239 (30 μg/kg), a selective α 1-adrenoceptor blocking drug, did not modify the heart rate in normotensive control (without pretreatment), bilaterally vagotomized and β blocked rats and in spontaneously hypertensive (SH) bilaterally vagotomized rats. Intracisternal (i.c.) administrations of AR-C 239 (30 μg/kg) however decreased the heart rate in normotensive β blocked and in SH bilaterally vagotomized rats. The differential effect of heart rate on i.c.v. versus i.c. administration of AR-C 239 suggests a brainstem localization of the α 1-adrenoceptors involved. The binding of [ 3H]prazosin was significantly higher in homogenates from whole brain and in membranes from the cerebral cortex and hypothalamus of SH rats as compared to normotensive rats. In addition, the binding of [ 125I]BE 2254, a new iodinated radioligand of high specific radioactivity used to characterize α 1-adrenoceptors, was significantly increased in membranes from the NTS of SH rats. These results suggest that central α 1-adrenoceptors localized in the brainstem and in the hypothalamus and the cortex play a role in the control of vagal tone in normotensive rats and of sympathetic activity in SH animals. Thus, it is postulated that central α 1-adrenoceptors may participate in either the genesis or the maintenance of genetic hypertension.

The role of β- and α-adrenoceptors in the regulation of the stages of the sleep-waking cycle in the cat

The effects of β-adrenergic drugs alone and in combination with α-adrenergic drugs on the stages of the sleep-waking cycle were studied in adult cats. Polygraphic sleep recordings of 16 h showed that prenalterol (20 and 40 mg/kg i.p.), a β 1-adrenoceptor-stimulating drug increased paradoxical sleep (PS) in a dose-related manner during 4–12 h. Salbutamol (40 mg/kg), a β 2-adrenoceptor-stimulating drug, decreased PS during the first 4 h. Metoprolol (10 and 50 mg/kg), a relatively selective β 1-adrenoceptor blocking drug, increased drowsy waking during the first 4 h. The larger dose also tended to decrease PS. Already at the lower dose metoprolol partially antagonized the PS increase produced by prazosin, an α 1-adrenoceptor blocking drug. Propranolol (5 mg/kg), a β 1-andβ 2-adrenoceptor blocking drug, which alone decreases PS, antagonized the PS increase induced by phentolamine, an α 1-andα 2-adrenoceptor drug. Atenolol (5 mg/kg), a poorly lipid-soluble β-adrenoceptor blocking drug, failed to counteract phentolamine in increasing PS. Metoprolol (10 and 50 mg/kg) and propranolol (5 mg/kg) clearly potentiated the increase in drowsy waking and decrease in deep slow wave sleep and PS induced by clonidine (0.01 mg/kg), an α 2-adrenoceptor-stimulating drug. The results support the involvement of β-adrenoceptors in the regulation of the sleep-waking cycle. A high level of β-adrenergic activity may facilitate the production of PS. A low level of β-adrenergic activity, especially in combination with a high level of α 2-adrenergic activity, may facilitate the production of drowsy waking. Central α 1-andβ 1-adrenoceptors may mediate opposite functions in the regulation of PS.

Possible role of central α1-adrenoceptors in the control of the autonomic nervous system in normotensive and spontaneously hypertensive rats

The cardiovascular effects of AR-C 239, a new and selective α 1-adrenoceptor blocking drug were studied in normotensive and spontaneneously hypertensive rats (SHR). AR-C 239 (300 μg/kg i.v.) did not change the heart rate in control (without pretreatment) and bilaterally vagotomized normotensive rats, but induced significant bradycardia in rats pretreated with a β-adrenoceptor blocking drug. This bradycardic effect was inhibited by atropine or bilateral vagotomy. In SHR, the administration of AR-C 239 reduced heart rate in the control, bilaterally vagotomized and β-blocked rats. Blood pressure was decreased in the same way in the two rat strains. It is suggested that central α 1-adrenoceptors could participate in the control of vagal tone in normotensive and SH rats, and of sympathetic activity in the SHR only.

Prejunctional inhibition mediated via alpha 2-adrenoceptors in excitatory transmission of canine small intestine.

Noradrenaline(NA) inhibited the contractile responses of longitudinal and circular muscles of canine small intestine to field stimulation (20 Hz, 1 ms, supramaximal voltage for 5 s). The purpose of this study was to see if NA-induced inhibitory action is mediated via alpha 1- or alpha 2-receptors and whether the inhibitory action involved prostaglandins. In both muscle layers the alpha 2-agonist, clonidine inhibited the contractile response to field stimulation more potently than did the alpha 1-agonists phenylephrine or methoxamine. It is suggested that NA-mediated prejunctional inhibition is mediated via alpha 2-receptors. Yohimbine, an alpha 2-adrenoceptor blocking drug antagonized NA-induced prejunctional inhibition, while E-643, an alpha 1-blocker, did not affect the inhibition. These results suggest that the inhibitory action of NA is mediated via alpha 2-receptors in both muscle layers. Indomethacin, an inhibitor of prostaglandin synthesis, did not affect NA-induced prejunctional inhibition in circular muscle, while augmenting it in longitudinal muscle. It is thought that NA-induced prejunctional inhibition is not mediated via prostaglandin release.

Enhancement of insulin secretion during selective blockade of alpha 1- and alpha 2-adrenoceptors in the rat: effects of somatostatin.

The effects of somatostatin on plasma concentrations of insulin and glucose in the presence of the selective alpha 1-adrenoceptor blocking agent prazosin or the selective alpha 2-adrenoceptor blocking drug yohimbine were studied in vivo in anesthetized rats. Infusion of both prazosin (0.080 mg/min) and yohimbine (0.018 mg/min) increased plasma insulin levels within 10 min. Prazosin, but not yohimbine, caused a significant increment in plasma glucose concentrations during the infusion of both prazosin and yohimbine, suggesting that the inhibitory effect of somatostatin is not mediated via a direct action on alpha 1- or alpha 2-adrenoceptors. Plasma glucose concentration fell slightly during somatostatin administration. A marked increment in insulin release occurred in response to cessation of the somatostatin infusion, both during prazosin- and yohimbine-treatment. We conclude that somatostatin efficiently inhibits insulin secretion during selective alpha 1- and alpha 2-adrenoceptor blockade and, further, that the insulin off-response after somatostatin treatment is potentiated by alpha-adrenoceptor blockade. This study also indicates that blockade of alpha 1- as well as alpha 2-adrenoceptors leads to an increased insulin secretion.

Analysis of beta-adrenoceptors mediating renin release produced by isoproterenol in conscious dogs.

Types of beta-adrenoceptors mediating renin release induced by isoproterenol were investigated in conscious dogs. The nonselective beta-adrenoceptor blocking drugs propranolol, D-32, and pindolol significantly inhibited increases in heart rate and plasma renin activity and a fall of blood pressure produced by intravenous infusion of isoproterenol (10 microgram . kg-1 . 20 min-1). d-Propranolol and d-D-32 did not inhibit these three responses to isoproterenol. The selective beta 1-adrenoceptor blocking drug atenolol, at the oral dose of 6 mg/kg, which selectively suppressed isoproterenol-induced tachycardia, significantly inhibited the renin release caused by isoproterenol. By contrast, the renin release induced by isoproterenol was not modified by the selective beta 2-adrenoceptor blocking drug IPS-339 at an oral dose of 3 mg/kg, which fully and selectively antagonized the fall of blood pressure in response to isoproterenol. There was good correlation between suppression of isoproterenol-induced renin release and that of isoproterenol-induced tachycardia after various beta-adrenoceptor blocking drugs. These results lead to the conclusion that in conscious dogs the beta-adrenoceptors mediating release are mainly of the beta 1 type.

COMPARISON OF LABETALOL, HYDRALLAZINE, AND PROPRANOLOL IN THE THERAPY OF MODERATE HYPERTENSION

The efficacy of labetalol, an alpha and beta adrenoceptor blocking drug, has been compared with that of placebo, of propranolol alone, of hydrallazine alone, and of hydrallazine plus propranolol in combination in a randomized double-blind, fixed-dose crossover trial. Labetalol (300 mg twice a day) was equally effective with propranolol (80 mg twice a day), and more effective than hydrallazine (50 mg twice a day) alone. The effect of labetalol was comparable with that of hydrallazine plus propranolol when the patient was standing, but less potent with the patient in the supine position. Side effects were few.