Β-adrenergic Receptor Blocking Drugs Research Articles

The effect of some beta-adrenergic receptor blocking drugs on carbohydrate metabolism in mouse brain.

There was no clear relationship between the peripheral β-blocking properties of the drugs studied and their effects on brain carbohydrate metabolism. Five types of action on brain carbohydrate metabolism have been observed. 1. (a) increased glucose uptake and glycogenesis and decreased glycolysis (propranolol) 2. (b) increased glycogenesis and reduced glycolyis without glucose uptake being affected (INPEA, LB 46 and dl -alprenolol) 3. (c) increased glycogenesis without affecting glucose uptake or glycolysis (desoxypropranolol) 4. (d) increased glycogenolysis and glycolysis ( d -alprenolol) 5. (e) increased glycogenolysis without affecting glycolysis (sotalol). Practolol did not have an effect on any of the parameters of brain carbohydrate metabolism studied.

Effects of the adrenergic receptor blocking agents on the ganglionic transmission

The effects of α- and β-adrenergic receptor blocking drugs given intra-arterially or intravenously were investigated on the postganglionic action potentials evoked by repetitive preganglionic stimulation of varying intensity in the in situ superior cervical ganglion preparation of the rabbit. When injected intra-arterially to the ganglion dihydro-erogotamine was usually ineffective in altering ganglionic transmission whereas phentolamine did cause a marked depression. Both drugs blocked the inhibitory action of norepinephrine on the transmission. These α-blockers produced a transient partial inhibition in ganglion transmission when injected intravenously at conventional doses. The β-blockers, propranolol, pronethalol and sotalol, depressed ganglionic transmission markedly when injected intra-arterially. However, only the latter drug was found to depress transmission when it was given intravenously at doses adequate to block β-receptors in the other structures. The results do not favor any hypothetical modulatory action of catecholamines in ganglionic transmission.

The combined effect of atropine and β-adrenergic receptor antagonists on left ventricular function and coronary blood flow

The effect on the ability of the left ventricle to perform work of two β-adrenergic receptor blocking drugs, dl-propranolol (Inderal) and Ciba 39,089-Ba (Trasicor), with and without atropine, has been studied over a wide range of work. Equipotent β-blocking doses of both drugs were used. Both dl-propranolol and Ciba 39,089-Ba depressed left ventricular function curves and displaced them to the right, indicating a decrease in the ability of the left ventricle to perform work at a given filling pressure. The depressant effect of dl-propranolol was significantly greater than that of an equipotent β-blocking dose of Ciba 39,089-Ba. Both β-antagonists caused a decline in coronary blood flow, in heart rate, and in the rate at which O 2 was extracted from the coronary circulation. Each increased the amount of work done by the myocardium per unit of oxygen extracted from the coronary circulation. The depressant effect of either dl-propranolol or Ciba 39,089-Ba on the ability of the left ventricle to perform work at a given filling pressure was not modified by atropine.

Analysis of the central vasomotor effects of choline

Choline injected into the lateral cerebral ventricle (ICV) of the anesthetized dog produced biphasic vasomotor effects. There was an initial short-lasting pressor response which was blocked by atropine and reduced by bilateral adrenalectomy. This was followed by a delayed secondary depressor response which was absent in dogs pretreated with reserpine (1 eV) or tetrabenazine (i.p.). The depressor response was blocked by ICV administration of β-adrenergic receptor blocking drugs. A central cholinergic action leading to a peripheral sympathoadrenal discharge appears to be responsible for the initial pressor phase. The delayed depressor phase was attributed to a central action of catecholamines released from central neural structures.

Myocardial and local anesthetic actions of β-adrenergic receptor blocking drugs: Relationship to physicochemical properties

In 19 compoundsstudied, there was no simple relationship between β-blocking potency, lipoid solubility, pK a, or propensity for depressing myocardial contraction. No correlation existed between lipoid solubility and negative inotropism on isolated rabbit atria. Pronethalol and propranolol (CHCl 3/H 2O partition ratios: 15 and 34.5, respectively) showed strong local anesthetic effects (rabbit cornea test) while MJ-1999 and INPEA (CHCl 3/H 2O partition ratios: 0.03 and 1.29, respectively) were completely devoid of this action. That lipoid solubility is not solely involved, however, is evidenced by compound Kö-592 which has a partition ratio of 0.096, yet still has significant local anesthetic actions. The weak β-blocker (+)-propranolol showed almost the identical local anesthetic as the more potent racemate, suggesting a minimum of complementarity between this drug and the receptor system mediating local anesthesia. It also indicates that β-blocking potency per se is not involved in this effect. The (−)/(+) isomer ratios of activity ranged from 15 to 50 for myocardial β-blocking effects.

Relation between β-adrenergic blocking potency and cardiotoxicity in a series of β-adrenergic receptor blocking drugs

Relation between β-adrenergic blocking potency and cardiotoxicity in a series of β-adrenergic receptor blocking drugs