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PubMed1971

Effect of beta-adrenoceptive blocking agents on the response to bronchoconstrictor drugs in the guinea-pig air overflow preparation. Appendix describing a new modification of the air overflow method.

1. Propranolol augmented the bronchoconstrictor response to methacholine or histamine, recorded by air overflow in the anaesthetized, vagotomized guinea-pig.2. After adrenalectomy, propranolol was still active, though less so than before.3. In the pithed guinea-pig, there was no augmentation of the effect of bronchoconstrictors on air overflow. The action of propranolol could thus be due to the beta-adrenoceptor blockade of compensatory sympathetic bronchodilator activity, as concluded by McCulloch, Proctor & Rand (1967).4. Electrical stimulation of the thoracic region of the spinal cord of the pithed guinea-pig reduced the effect of bronchoconstrictors on air overflow. This reduction could be blocked by propranolol; practolol was much less effective.

Acetanilides↗
PubMed1972

Negative inotropic responses of the isolated heart of the rat to isoprenaline.

The isolated heart of the rat perfused at 38 degrees C responded to isoprenaline with an initial positive inotropism followed by a bi-phasic negative inotropic effect. The latter was associated with the simultaneous biphasic rate increase. On reduction of the perfusion temperature to 20 degrees C, isoprenaline no longer increased the rate but a negative inotropic response remained. Blockade of this by practolol suggested that it was mediated via beta(1)-adrenoceptors.

Acetanilides↗
PubMed1973

The detection of differential beta-adrenoceptor blockade in the cat.

1. Tachycardia and bronchodilatation were produced by intravenous dimethylphenylpiperazinium iodide (DMPP) in the spinal or pithed cat. Responses other than those involving beta-adrenoceptors were minimized by appropriate blocking agents.2. With intact adrenals, both the tachycardia and bronchodilatation with 10 mug/kg DMPP were equal to those with 1 mug/kg adrenaline.3. After adrenalectomy, tachycardia with 100 mug/kg DMPP was equal to that with 1.5 mug/kg adrenaline, but the bronchodilatation was equal to that with only 0.3 mug/kg. This difference may reflect the relative activity of the sympathetic supply to the organs.4. After adrenalectomy, propranolol was 3 times as effective against bronchodilatation due to DMPP as against tachycardia. Practolol was inactive against bronchodilatation.5. With intact adrenals, propranolol reduced both tachycardia and bronchodilatation due to DMPP equally. Propranolol also antagonized equally both effects of adrenaline in the pithed cat after adrenalectomy.6. In the spinal cat, propranolol caused bradycardia and bronchoconstriction that persisted after adrenalectomy or pithing. It was reduced by pempidine and guanethidine and is attributed to spontaneous adrenergic neuronal activity.7. The Appendix describes a device for cycle-by-cycle spirometry and correction for zero drift of a micromanometer, used in this study for the continuous recording of bronchial resistance.

Adrenalectomy↗
PubMed1976

Mechanism of the indirect sympathomimetic effect of 5-hydroxytrypt-amine on the isolated heart of the rabbit.

1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP). 2 The cardiac stimulant effects of 5-HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist. 3 Responses to 5-HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6-hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated. 4 Rapid, reversible and selective tachyphylaxis to 5-HT was demonstrated during perfusion with 5-HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5-HT were also reduced. 5 Perfusion of hearts with colchicine inhibited stimulant responses to 5-HT and DMPP but had little effect on responses to noradrenaline or tyramine. 6 Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5-HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine. 7 Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5-HT and DMPP unaffected. 8 5-HT, tyramine and DMPP evoked 3H-release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3H]-(-)-noradrenaline. The pattern of release evoked by 5-HT was similar to that of DMPP but differed from that of tyramine. 9 Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/1 did not affect 3H-overflow after tyramine but greatly inhibited that evoked by 5-HT and DMPP. 10 The results confirm that the stimulatn effects of 5-HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium-dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement).

Animals↗
PubMed1976

The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea.

1 A new in vitro preparation, the isolated lung strip of the cat, is described for investigating the direct effect of drugs on the smooth muscle of the peripheral airways of the lung. The preparation comprises a thin strip of lung parenchyma which can be mounted in a conventional organ bath for isometric tension recording. Its pharmacological responses have been characterized and compared with the isolated tracheal preparation of the cat. 2 The lung strip exhibited an intrinsic tone which was relaxed by catecholamines, aminophylline and flufenamate. It was contracted strongly by histamine, prostaglandin F2alpha, acetylcholine, compound 48/80, potassium depolarizing solution and alternating current field stimulation. In contrast, the cat trachea was unresponsive to histamine and prostaglandin F2alpha and did not exhibit an intrinsic tone. 3 (-)-Isoprenaline and (-)-adrenaline were much more potent in relaxing the lung strip than the trachea. The potency order of relaxation responses to isoprenaline, adrenaline and (+/-)-noradrenaline in the lung strip was isoprenaline greater than adrenaline greater than noradrenaline but in the trachea was isoprenaline greater than noradrenaline greater than or equal to adrenaline. 4 beta2-Adrenoceptor selective agonists salbutamol and terbutaline were more potent in the lung strip than the trachea, suggesting beta2-adrenoceptors predominated in the lung strip. Propranolol was equipotent in inhibiting isoprenaline relexations of the lung strip and trachea, whereas practolol was much less effective in inhibiting lung strip than trachea, further supporting a predominance of beta2-adrenoceptors in lung strip and beta1-adrenoceptors in trachea. 5 Strong Schultz-Dale type contractions were elicited in both lung strips and trachea by Ascaris lumbricoides antigen in actively sensitized cats. The initial phase of the contractile response of the lung strip following challenge was shown to be due to histamine release and was absent in the trachea. The delayed phase of the contraction which took several minutes to develop in both the mepyramine-treated lung strip and trachea was not due to prostaglandins E1, F2alpha or bradykinin, the probable mediator being slow reacting substance of anaphylaxis (SRS-A). 6 It is concluded that the isolated lung strip of the cat is useful as an in vitro model for investigating the effect of drugs on the smooth muscle of the peripheral airways of the lungs.

Adrenergic beta-Agonists↗
PubMed1977

An inhibitory role for noradrenaline in the mouse vas deferens.

1 Noradrenaline (0.1-3.0 muM) inhibited the twitch responses to single pulse field stimulation of the isolated vas deferens of the mouse. The higher concentrations of noradrenaline (ca. 0.3-3.0 muM) were required to make the tissue contract.2 Phentolamine (10 muM) abolished the contractor response to higher concentrations of noradrenaline and antagonized the inhibitory effect of lower concentrations on the twitch response.3 Propranolol (10 muM) potentiated both the contractor and the inhibitory effect of noradrenaline on the twitch response.4 Isoprenaline (0.1-3.0 muM) and salbutamol (1.0-3.0 muM) both inhibited the twitch response. Their effects were antagonized by propranolol (10 muM), but not by practolol (10 muM).5 The effects of uptake(1) and uptake(2) blocking agents were determined. Cocaine (10 muM) reduced the size of the twitch response in 2 out of 4 experiments. Imipramine (0.18 muM) also reduced the size of the twitch, as did oestradiol (3.7 muM) and a combination of cocaine and oestradiol.6 Contractor responses to exogenous noradrenaline showed tachyphylaxis, but when this was not very marked, the response could be shown to be potentiated by uptake blocking agents.7 The inhibitory effect of noradrenaline on the twitch response was greatly potentiated by cocaine (10 muM) and much less so by oestradiol (3.7 muM).8 It is concluded that the transmitter responsible for the twitch response is either an unknown substance released from the sympathetic neurone, or noradrenaline acting upon a receptor with none of the characteristics of known alpha- or beta-adrenoceptors. In either case, noradrenaline can inhibit the output, probably by stimulation of presynaptic alpha-adrenoceptors.

Albuterol↗
PubMed1978

Characterization of the adrenoceptor in the isolated cremaster muscle of the guinea-pig.

1 Contractions of the isolated cremaster muscle of the guinea-pig obtained in response to direct electrical stimulation were augmented by salbutamol, isoprenaline, adrenaline, noradrenaline and orciprenaline (in that order of potency), and by potassium chloride. Phenylephrine and xylometazoline had no effect. 2 The augmenting effect of isoprenaline on the twitch response was not altered by yohimbine or tolazoline, but was totally prevented by butoxamine, (--)-1-(4-nitrophenyl)-2-isopropylamino-ethanol (INPEA), (+/-)-INPEA, sotalol, metalol and practolol; (+)-INPEA was much less effective. The augmenting effect of potassium was not altered by beta-adrenoceptor blockade. 3 The results are consistent with the view that the augmenting effect of the sympathomimetic agents is mediated through beta2-type of adrenoceptor in the skeletal muscle fibres.

Animals↗
PubMed1978

Inhibition of [3H]-dihydroalprenolol binding to rat cardiac membranes of various beta-blocking agents.

Binding of [3-H]-dihydroalprenolol ([3-H]-DHA) to rat cardiac membranes was rapid and reversible (k1 = 0.633-0.701 x 10(6) M(-1) S(-1) And k(-1) = 0.0017-0.0043 s(-1). 2 [3-H]-DHA bound to a single class of binding sites with an equilibrium dissociation constant (Kd25degreesc) of 5.7+/-1.1 x 10(-9) M. 3 This binding was specific and the order of potency of adrenoceptor agonists in competing for the binding sites was (-)-isoproterenol greater than (+/-)-isoproternol greater than (+)-isoproterenol greater than (-)-adrenaline greater than (-)-noradrenaline. This was in agreement with the beta1 nature of the cardiac beta-receptors. 4 Cardioselective beta-blockers (i.e. metoprolol, acebutolol and practolol) were shown to have lower binding site affinities, when compared to other blockers. This may be related to steric hindrance by the side-chain at the aromatic end of these molecules.

Adrenergic beta-Antagonists↗
PubMed1978

beta-Adrenoceptor antagonists inhibit the behavioural responses of rats to increased brain 5-hydroxytryptamine.

1 The effect of various beta-adrenoceptor blocking agents on the 5-hydroxytryptamine (5-HT)-induced hyperactivity response produced in rats by administration of tranylcypromine (10 mg/kg i.p.) followed by L-tryptophan (50 mg/kg i.p.) has been investigated. 2 (+/-)-Alprenolol, (+/-)-timolol, (+/-)-sotalol, (+/-)-pindolol (all at 40 mg/kg) all inhibited the hyperactivity response to some degree when given 45 min before the tranylcypromine, as did (+/-)-oxprenolol when given after the L-tryptophan. 3 beta-Adrenoceptor antagonists that are not found in the brain appreciable amount after peripheral injection, (+/-)-atenolol, (+/-)-practolol, (+/-)-labetalol and (+/-)-acebutalol, did not inhibit the 5-HT-mediated behaviour. 4 Neither the beta1-selective drug (+/-)-metoprolol, nor the beta2-selective drug (+/-)-butoxamine inhibited the behavioral response. 5 The drugs that blocked the 5-HT-mediated behaviour did not alter brain 5-HT concentrations, synthesis rate or the accumulation of 5-HT following tranylcypromine/L-tryptophan. However, they did inhibit the hyperactivity produced by the suggested 5-HT agonist, 5-methoxy N,N-dimethyltryptamine, indicating that the beta-adrenoceptor blocking drugs were inhibiting the post-synaptic 5-HT-mediated response. 6 Circling produced by methamphetamine (3 mg/kg) in unilateral nigro-striatal lesioned rats was not altered by alprenolol, sotalol, pindolol or metaprolol, indicating that these drugs do not alter dopamine-mediated behaviour. 7 It is concluded that non-selective (beta1 and beta2) adrenoceptor antagonists which have a high brain/blood ratio following their peripheral injection, block 5-HT-mediated behavioural responses in the rat.

Adrenergic beta-Antagonists↗
PubMed1979

Investigation of the mechanism of propranolol-induced bronchoconstriction.

1 Dose-related increases in airways resistance (Raw) and decreases in dynamic lung compliance (Cdyn) were recorded in guinea-pigs and rats following intravenous injection of propranolol and of the cardioselective beta-adrenoceptor blocking drugs, atenolol and practolol. 2 The bronchoconstriction reached a peak in 2 to 4 min and subsided within 15 min. Repeated injections caused identical responses in the airways. 3 The isomer (+)-propranolol, which has only weak beta-adrenoceptor blocking activity, produced identical responses when given alone or when given after a dose of the racemate, sufficient to cause measurable beta-adrenoceptor blockade in the lungs. 4 After the initial bronchospasm had subsided, the beta-adrenoceptor blocking drugs and the isomer, (+)-propranolol, produced potentiation of the bronchoconstrictor effects of 5-hydroxytryptamine and histamine. 5 Both the bronchospasm and the potentiation occurred in adrenal demedullated rats. 6 The results indicate that the bronchoconstrictor effects of these drugs are unrelated to beta-adrenoceptor blockade in the airway smooth muscle.

Adrenal Medulla↗
PubMed1980

Adaptational responses to prolonged beta-adrenoceptor blockade in adult rabbits.

1 A method for measuring propranolol concentrations in plasma has been modified to permit estimations to be made on small volumes. The method has been used to correlate blockade of heart rate increases in response to intravenous isoprenaline, in both young and adult rabbits, with plasma concentrations of propranolol after subcutaneous injections of 2 or 4 mg/kg. It has been found that the relation between beta-adrenoceptor blockade and plasma concentrations is the same in rabbits as that determined by previous workers in man. 2 Adult Dutch dwarf rabbits were treated for 9 weeks twice daily subcutaneously with 2 mg/kg propranolol, or 10 mg/kg practolol, or with saline. 3 The treatment caused no change in heart weight in relation to body weight or in the water content of the hearts, in contrast to effects previously observed in young rabbits. 4 As in the young rabbits, treatment did cause a prolongation of action potential duration, as measured with intracellular electrodes in hearts of animals killed 24 h after the last dose of drug. 5 In another series of experiments, with a similar regime of treatment for 6 weeks, a significant reduction of diastolic blood pressure was observed in the propranolol group. 6 During the course of treatment and at the end, there was no change in the heart-rate increases observed in response to intravenous isoprenaline administered not less than 15 h after the previous dose of beta-blockers. Thus no functional alteration in sensitivity ot beta-adrenoceptor stimulation was apparent.

Adaptation, Physiological↗
PubMed1980

Preliminary pharmacological characterization of the bovine isolated bronchial artery strip: a new preparation.

1 This paper describes a preliminary pharmacological study of the isolated helical strip of bovine bronchial artery under isotonic conditions in Krebs-Henseleit solution. 2 The tissue contracted to histamine and 5-hydroxytryptamine (5-HT), actions which were selectively antagonized by mepyramine and methysergide respectively. Histamine was not inhibited by metiamide and 5-HT was not affected by morphine. 3 Slow reacting substance of anaphylaxis (SRS-A), prostaglandin F2 alpha (PGF2 alpha) and PGE2 were spasmogenic, whereas PGE1 caused relaxation. No potential antagonists of these agents were tested. 4 Carbachol, at all concentrations, caused contractions of the bronchial artery which were completely, irreversibly blocked by atropine. 5 The spasmogenic action of phenylephrine was selectively blocked by dibenamine. Vessel strips which were partially contracted to histamine, relaxed to isoprenaline and salbutamol. The action of isoprenaline was inhibited similarly by either propranolol or practolol. The evidence therefore suggests the presence of functional alpha, beta 1 and beta 2-adrenoceptors.

Animals↗
PubMed1980

The stimulatory effects of neurotensin and related peptides in rat stomach strips and guinea-pig atria.

1 The stimulatory effects of neurotensin (NT) and several NT fragments were evaluated in two pharmacological preparations: rat stomach strips and isolated spontaneously beating atria of guinea-pigs.2 In rat stomach strips, NT elicited a dose-dependent contractile effect in concentrations varying between 1.3 x 10(-9) and 5.4 x 10(-7) M.3 The contractile effect of NT (1.3 and 5.4 x 10(-8) M) in this tissue was not modified by atropine (3.4 x 10(-7) M), methysergide (2.0 x 10(-6) M), a mixture of cimetidine (8.0 x 10(-6) M) and diphenhydramine (7.8 x 10(-6) M), indomethacin (1.4 x 10(-5) M), 8-Leu-angiotensin II (1.0 x 10(-6) M), glucagon (2.0 x 10(-6) M) or somatostatin (3.0 x 10(-7) M).4 Rat stomach strips desensitized by bradykinin (6.1 x 10(-6) M) or substance P (7.4 x 10(-6) M) maintained their sensitivities to NT (1.3 and 5.4 x 10(-8) M).5 In guinea-pig atria, NT produced a dose-dependent positive inotropic action in concentrations varying between 5.4 x 10(-10) and 2.7 x 10(-7) M.6 The inotropic effect of NT (2.7 x 10(-9) M) was not influenced by methysergide (2.8 x 10(-6) M), atropine (3.4 x 10(-7) M), practolol (1.5 x 10(-5) M), 8-Leu-angiotensin II (1.0 x 10(-6) M), or indomethacin (1.4 x 10(-5) M), but it was reduced by 37% by cimetidine (4.0 x 10(-5) and 2.0 x 10(-4) M). A combination of cimetidine (4.0 x 10(-5) M) and diphenhydramine (3.9 x 10(-6) M) did not produce a greater inhibition of NT than cimetidine alone.7 Atria desensitized by bradykinin (6.1 x 10(-6) M) or glucagon (2.0 x 10(-6) M) maintained their sensitivities to NT (2.7 x 10(-9) M). Substance P was inactive both as an agonist or antagonist of NT.8 These results suggest the existence of specific NT receptors in rat stomach strips and guinea-pig atria.9 The data derived from our structure-activity study suggest that the minimum structure required for the full stimulation of NT receptors in these two preparations is H-Arg(9)-Pro(10)-Tyr(11)-Ile(12)-Leu(13)-OH. The sequence PyroGlu(1)-Leu(2)-Tyr(3)-Glu(4)-Asn(5)-Lys(6)-Pro(7)-Arg(8)- and the amino acids Ile(12) and Leu(13) appear to contribute mainly to the affinity or binding of NT to its receptor. The chemical groups responsible for the full activation (intrinsic activity) of NT receptors seem to be located in the sequence -Arg(9)-Pro(10)-Tyr(11).

Animals↗
PubMed1980

Comparison of the anti-hypertensive response to beta-adrenoceptor blocking drugs in intact and adrenal-demedullated spontaneously hypertensive rats.

1 The beta-adrenoceptor blocking drugs atenolol, metoprolol, practolol, propranolol, timolol and oxrenolol (as racemates) were administered acutely at three dose levels (0.01, 0.03 and 0.1 mmol/kg i.p. or s.c.) to spontaneously hypertensive rats with intact adrenal glands (SH-rats) and following unilateral adrenalectomy and contralateral adrenal-demedullation (SHAD-rats). Changes in mean arterial pressure and heart rate were determined via an indwelling aortic catheter, with the animals placed in a quiet environment. 2 All drugs significantly lowered the blood pressure of SHAD-rats, and these responses were not always associated with changes in basal heart rate. 3 With the exception of metoprolol and atenolol, the beta-adrenoceptor blocking drugs were less effective as anti-hypertensives in SH- than in SHAD-rats. Notably, timolol and oxprenolol lowered the blood pressure of SH-rats at low doses only, whereas propranolol evoked a pressor response in this model. 4 Whilst (+)-propranolol lowered the blood pressure of SHAD-rats only at a dose which caused myocardial depression, the anti-hypertensive response to (--)-propranolol did not parallel changes in heart rate and was preceded by a pressor response. 5 The results imply that adrenal catecholamine release contributes towards masking the anti-hypertensive effects of some beta-adrenoceptor antagonists in SH-rats.

Adrenal Medulla↗
PubMed1980

In vitro activity of RO363, a beta1-adrenoceptor selective agonist.

1 The beta-adrenoceptor stimulant effects of RO363 and (--)-isoprenaline have been compared in a variety of isolated tissue preparations. 2 RO363 is approximately half as potent as (--)-isoprenaline in tissues where actions are due to beta1-receptor activation (guinea-pig atrial and ileal preparations and ventricular strips from the rabbit, rat and guinea-pig. 3 In uterine and lung strip preparations from the guinea-pig, where responses are due to beta2-receptor stimulation. RO363 is 100 to 350 times less active than (--)-isoprenaline and has a low intrinsic activity. 4 In spontaneously contracted tracheal preparations from the guinea-pig, RO363 is a full agonist and is approximately half as potent as (--)-isoprenaline. These effects of RO363 are due to the activation of a population of beta1-receptors in the tissue since RO363 and (--)-isoprenaline have the same relative potencies in trachea, cardiac and ileal preparations. In addition the Kb values for practolol are similar in all these preparations when RO363 is used as the agonist. 5 The results show that RO363 is a potent and highly selective beta1-receptor agonist.

Adrenergic beta-Agonists↗
PubMed1980

Relationship between the (--)-[3H]-dihydroalprenolol binding to beta-adrenoceptors and transmembrane 86Rb efflux of the BC3H1 nonfusing muscle cell line.

1 We have studied the binding properties of the beta-adrenoceptor antagonist [3H]-dihydroalprenolol ([3H]-DHA) on a membrane preparation of the non-fusing muscle cells BC3H1. 2 [3H]-DHA appears to bind to two classes of sites. The first site has a high affinity (KD = 0.53 nM) and a low capcity (Bmax = 58 fmol/mg of protein). The second site has a low affinity (KD = 110 nM) and a high capacity (Bmax = 1100 fmol/mg of protein). 3 The pharmacological properties of the high affinity low capacity site correspond to the known properties of the beta 2-adrenoceptors since the agonists inhibit [3H]-DHA binding following the series isoprenaline greater than adrenaline greater than noradrenaline greater than phenylephrine and the antagonists following the series alprenolol congruent to propranolol greater than butoxamine greater than practolol greater than phentolamine. 4 The binding properties of the beta-adrenoceptors were correlated with the effect of beta-adrenoceptor agonists and antagonists on 86Rb efflux rate from BC3H1 Cells. 5 There is very good correlation between the dissociation constants obtained by inhibition of [3H]-DHA binding by the antagonists alprenolol and propranolol, and the inhibition constants calculated from their antagonism of the 86Rb efflux rate stimulation by adrenaline. The ratio of the dissociation constants obtained by inhibition of [3H]-DHA binding by agonists and their EC50, calculated from 86Rb efflux curves, is higher than 1. This high KD/EC50 ratio indicates a high coupling efficiency between receptor occupancy by agonists and the biological effect measured.

Adrenergic beta-Agonists↗
PubMed1980

Adrenaline activation of prejunctional beta-adrenoceptors in guinea-pig atria.

1. Adrenaline in a concentration of 1.0 microM depressed the stimulation-induced efflux of tritium from the guinea-pig atria incubated with [3H]-noradrenaline, whereas adrenaline in a concentration of 0.5 nM significantly enhanced the stimulation-induced efflux of tritium. This enhancement was blocked by metoprolol (0.1 microM) and thus appears to be mediated by beta-adrenoceptors. 2. In guinea-pig atria incubated with unlabelled adrenaline and then with [3H]-noradrenaline, both catecholamines were released by field stimulation. In such atria metoprolol, practolol, oxprenolol or propranolol decreased the stimulation-induced efflux of tritium. These effects did not occur if the atria were incubated with unlabelled noradrenaline and then with [3H]-noradrenaline, suggesting that neuronally released adrenaline activates prejunctional beta-adrenoceptors. 3. The effect of oxprenolol in decreasing the release of tritium from guinea-pig atria, incubated with unlabelled adrenaline and then with [3H]-noradrenaline was greater in the presence of phentolamine. This may reflect the alpha-adrenoceptor blocking activity of oxprenolol.

Animals↗
PubMed1980

Evaluation of antagonism of aconitine-induced dysrhythmias in mice as a method of detecting and assessing antidysrhythmic activity.

1 Antagonism of aconitine-induced dysrhythmias in mice as a method of detecting and assessing antidysrhythmia activity was evaluated. 2 Aconitine-induced dysrhythmias in mice appear to be selectively sensitive to antidysrhythmia agents (administered intraperitoneally) which reduce the inward sodium current in cardiac cells. 3 Antidysrhythmic agents whose mechanism of action is thought to depend on beta-adrenoceptor blockade, prolongation of cardiac monophasic action potentials or calcium antagonism are ineffective in delaying the onset of aconitine-induced dysrhythmias in mice. The inactive drugs were practolol, sotalol, bretylium, amiodarone and verapamil. 4 Comparisons of anti-dysrhythmic activities of test drugs should be based on more than one ED value and should take account of efficacy as well as potency. 5 The mouse aconitine test is a useful and rapid method of evaluating oral antidysrhythmic activity in terms of potency, efficacy and duration of action. 6 With respect to potency, efficacy, oral activity, duration of action and safety, 3 alpha-amino-5 alpha-androstan-2 beta-ol-17-one hydrochloride (Org 6001) offered the most satisfactory overall profile of the active drugs tested (Org 6001, aprindine, quinidine, disopyramide, lignocaine, mexiletine, procainamide and propranolol).

Aconitine↗