Measurement of hydrophobicity, surface activity, local anaesthesia, and myocardial conduction velocity as quantitative parameters of the non-specific membrane affinity of nine ?-adrenergic blocking agents

Hellenbrecht, D.; Lemmer, Björn; Wiethold, G.; Grobecker, H.

doi:10.1007/bf00501161

Cited by 146 publications

(39 citation statements)

References 14 publications

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“…3). These results are in agreement with the findings of Hellembrecht et al (13) who assessed the local anesthetic activity of 9-adrenergic blocking drugs on extracellular action potential of frog sciatic nerve.…”

Section: Methodssupporting

confidence: 93%

Comparative Study of the Secretory Response to Dopamine and Seven Amino Acid Conjugated Derivatives on the Blood-Perfused Canine Pancreas

Ishida

Sasa

Takaori

1980

Japanese Journal of Pharmacology

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Abstract-The actions of f3-adrenergic blocking drugs, propranolol, pindolol, timolol, carteolol, sotalol and practolol, were examined regarding effects on crayfish giant axon in an attempt to determine the relationship among chemical structure and local anes thetic activity, and the interaction of these drugs with Ca++. The activities of local anesthetics such as procaine and lidocaine served for comparisons.A conventional microelectrode technique was used to obtain the resting membrane and action poten tials. All drugs except sotalol and practolol dose-dependently inhibited the dV/dt and amplitude of the action potential with a slight decrease (less than 6 mV) in the resting membrane potential.The relative potencies of these drugs in the reduction of the dV/dt were as follows: propranolol 13.3, pindolol 1.7, procaine 1.0, lidocaine 0.91, timolol 0.71 and carteolol 0.22. Sotalol and practolol had little activity. The chemical structure of the drugs for local anesthetic action was closely related to that of the lipophilic aromatic group; the most potent activity seen in the naphthyl group. Potentiation of the local anesthetic activity in low Ca solution was obtained with pindolol, timolol, carteolol, sotalol and practolol. Reduction of the activity in high Ca++ solution was observed with propranolol, pindolol, timolol, procaine and lidocaine. These results suggest that external Ca++ competes with the local anesthetic action of the (3-adrenergic blocking drugs, at the site of the action potential generating mechanism.

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Section: Methodssupporting

confidence: 93%

Comparative Study of the Secretory Response to Dopamine and Seven Amino Acid Conjugated Derivatives on the Blood-Perfused Canine Pancreas

Ishida

Sasa

Takaori

1980

Japanese Journal of Pharmacology

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“…Likewise, metoprolol failed to inhibit ODC elevation after adrenaline in granulosa cells (Veldhuis et al, 1980). The low membrane stabilizing activity of metoprolol is correlated with its moderate lipophilic properties compared to propranolol (Hellenbrecht, Lemmer, Wiethold & Grobecker, 1973 (Ablad, Borg, Carlsson, Ek, Johnsson, Malmfors & Regardh, 1975;Johnsson, Regardh & Solvell, 1975). The dose used in these studies was approximately 10 times the mg/kg dose which purportedly blocks 12-receptors in humans, and yet this dose failed to inhibit the agonist-induced ODC activity.…”

Section: Resultsmentioning

confidence: 92%

β₂‐ADRENOCEPTORS REGULATE INDUCTION OF MYOCARDIAL ORNITHINE DECARBOXYLASE IN MICE in vivo

Copeland¹,

Larson²,

Roeske³

et al. 1982

British J Pharmacology

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The pharmacological characteristics of the myocardial adrenoceptor of the mouse have been examined during embryogenesis by measuring ornithine decarboxylase (ODC, EC 4.1.1.17) induction. A four fold elevation of ODC activity was observed after isoprenaline (10 mg/kg, s.c), and enzyme activity was increased two to three fold following adrenaline (1 mg/kg, s.c.) or terbutaline given by direct injection to the foetus (10 μg/500 mg). Pretreatment with the β‐adrenoceptor antagonist, propranolol (10 mg/kg), totally blocked the increase in ODC activity. Elevation of myocardial ODC activity was not inhibited by metoprolol, a relatively specific β1‐adrenoceptor antagonist, at a dose of 10 mg/kg. Since the increase in ODC activity was blocked by a β‐adrenoceptor antagonist (propranolol) and enzyme activity was stimulated by terbutaline, a β2‐agonist, we conclude that β2‐adrenoceptors are selectively coupled to the regulation of murine cardiac ODC activity following catecholamine stimulation.

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“…The observation that the (+)-and (-)-isomers of propranolol were equipotent in inhibiting lymphocyte capping (Figure 2) is consistent with this action being due to the local anaesthetic and not the f-blocking properties of the drug. Moreover, using analogues of propranolol which also act as ,B-adrenoceptor antagonists, we observed inhibition of capping with those which exert local anaesthetic activity, alprenolol and oxprenolol, but not with those which are reported to have little or no such effect in other systems, metoprolol, sotalol and practolol (Singh & Vaughan Williams, 1970;Hellenbrecht et al, 1973;Ablad et al, 1975;Marshall et al, 1975; (Table 3). The concentrations of alprenolol and oxprenolol required to effect inhibition (5 x 1i-' M), were higher than that of propranolol (1o-3 M), whilst quinidine also inhibited capping when present at 10' M.…”

Section: Inhibition Of Transformationmentioning

confidence: 86%

“…Moreover transformation was shown to be consistently more sensitive than capping to all the membrane stabilizers included in this study. Thus, f-adrenoceptor antagonists such as practolol, and sotalol, with low partition co-efficients between n-octanol and phosphate buffer (pH 7.0) ( Table 1) (Hellenbrecht et al, 1973), and frequently considered to be without detectable membrane stabilising activity were capable of inhibition of transformation at higher concentrations (10-M).…”

Section: Discussionmentioning

confidence: 99%

“…In the presence of (Figure 1 and Table 1). Alprenolol proved only slightly less potent an inhibitor than propranolol, whereas metoprolol, practolol, and sotalol, analogues of propranolol commonly considered to be virtually devoid of local anaesthetic activity (Singh & Vaughan Williams, 1970;Hellenbrecht, et al, 1973;Ablad et al, 1975) (Singh & Vaughan Williams, 1970;Lemmer, Wiethold & Grobecker, 1973;Ablad et al, 1975;Marshall et al, 1977).…”

Section: Inhibition Of Transformationmentioning

confidence: 99%

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Inhibition of Lymphocyte Capping and Transformation by Propranolol and Related Compounds

Anderton

Axford

Cohn

et al. 1981

British J Pharmacology

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1 The effects of propranolol on phytohaemagglutinin (PHA)induced transformation of murine T lymphocytes and capping of anti-IgG on the surface of murine B lymphocytes have been examined. 2 A 50% inhibition of transformation was observed with 10-5 M propranolol, whereas a higher concentration, of the order of 10 -M propranolol was required to inhibit capping by 50%. The (+ ) and (-)-isomers of propranolol proved equipotent in these respects, and the relative potencies of selected analogues of propranolol (alprenolol, oxprenolol, metoprolol, practolol and sotalol) coincided with their potencies as membrane stabilizers; however, lymphocyte transformation was consistently more sensitive than capping.3 Similar effects were also seen with quinidine, chlorpromazine and lignocaine, and it was concluded that the inhibition of both lymphocyte functions was due to the membrane stabilizing actions of propranolol.

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Measurement of hydrophobicity, surface activity, local anaesthesia, and myocardial conduction velocity as quantitative parameters of the non-specific membrane affinity of nine ?-adrenergic blocking agents

Cited by 146 publications

References 14 publications

Comparative Study of the Secretory Response to Dopamine and Seven Amino Acid Conjugated Derivatives on the Blood-Perfused Canine Pancreas

Comparative Study of the Secretory Response to Dopamine and Seven Amino Acid Conjugated Derivatives on the Blood-Perfused Canine Pancreas

β₂‐ADRENOCEPTORS REGULATE INDUCTION OF MYOCARDIAL ORNITHINE DECARBOXYLASE IN MICE in vivo

Inhibition of Lymphocyte Capping and Transformation by Propranolol and Related Compounds

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Measurement of hydrophobicity, surface activity, local anaesthesia, and myocardial conduction velocity as quantitative parameters of the non-specific membrane affinity of nine ?-adrenergic blocking agents

Cited by 146 publications

References 14 publications

Comparative Study of the Secretory Response to Dopamine and Seven Amino Acid Conjugated Derivatives on the Blood-Perfused Canine Pancreas

Comparative Study of the Secretory Response to Dopamine and Seven Amino Acid Conjugated Derivatives on the Blood-Perfused Canine Pancreas

β2‐ADRENOCEPTORS REGULATE INDUCTION OF MYOCARDIAL ORNITHINE DECARBOXYLASE IN MICE in vivo

Inhibition of Lymphocyte Capping and Transformation by Propranolol and Related Compounds

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β₂‐ADRENOCEPTORS REGULATE INDUCTION OF MYOCARDIAL ORNITHINE DECARBOXYLASE IN MICE in vivo