Can chloropractolol alkylate β adrenoceptors?

  title={Can chloropractolol alkylate $\beta$ adrenoceptors?},
  author={Terry Kenakin and James W. Black},
EREZ et al.1 have classified chloropractolol as an irreversible, covalently-binding, antagonist of cardiac β adrenoceptors. This conclusion was based on the knowledge that similar halogen amides can alkylate sulphydryl groups2,3 and their observation that chloropractolol produced a long-lasting antagonism of β adrenoceptors associated with a depression of the maximum response to isoprenaline. 
8 Citations
Persistent beta-adrenoceptor blockade with alkylating pindolol (BIM) in guinea-pig left atria and trachea.
The actions of alkylating pindolol (N8-bromoacetyl-N1-3'-(4-indolyloxy)-2'-hydroxypropyl[z]-1,8- diamino-p-menthane; BIM) have been examined on beta-adrenoceptors in guinea-pig left atria and trachea and changes in the maximal density were determined. Expand
Irreversible β-adrenoceptor blockade of atrial rate and tension responses
Abstract The competitive reversible β-adrenoceptor antagonist activity of Ro 03-5255 [1-(acetylaminobenzfuran-2-yl)-2-isopropylaminoethanol] upon isoprenaline-induced increases of the rate andExpand
Cardiac beta-adrenergic receptor: evaluation of FM 24 as a new and very slowly dissociable blocker.
FM 24 is found to inhibit isoproterenol-dependent adenylate cyclase from rat cardiac particulate fraction with an apparent dissociation constant of 0.2 μM as compared to 0.01 μM for propranolol, which strongly suggest that FM 24 is a slowly dissociable β-receptor antagonist. Expand
Concentration-effect relationships with FM 24: a new long acting beta-adrenergic receptor antagonist.
The data are consistent with a prolonged duration of action due to a slow dissociation of the drug receptor complex, although an active metabolite of FM 24 cannot be excluded. Expand
Comparison of the apparent irreversible beta-adrenoceptor antagonist Ro 03-7894 with propranolol in cardiac ventricular muscle by pharmacological and radioligand binding techniques.
Scatchard analysis of the saturation curves for specific [3H]DHA binding showed that in the presence of propranolol, the displacement was characteristic of competitive antagonism, and apparent irreversible antagonism by Ro 03-7894 was also demonstrated in guinea-pig isolated papillary muscles. Expand
Disposition in rats and mice of chloropractolol, a new beta-blocking agent.
In the rat chloropractolol is extensively metabolized, which contrasts with the more limited metabolism of practolol in the same species, and a structure for the main urinary metabolite is suggested. Expand
The IN VIVO examination of the irreversible β‐adrenoceptor antagonist Ro 03‐7894 on cardiac rate and contractility
Two benzofuran‐2‐ethanolamines, which had previously been shown to exhibit respectively competitive and irreversible β‐adrenoceptor antagonism in guinea‐pig isolated atria, were compared in vivo using isoprenaline‐induced tachycardia of anaesthetized guinea-pigs and heart rate and contractility of open‐chest anaesthetics and of conscious cats. Expand
Nouvelles Syntheses du Chloropractolol: Marquage au 14C, 2H, 3H
Le chlorure de l'acide chloracetique(1-14C a ete obtenu, avec de bons rendements, par reaction d'echange entre le chlorure de benzoyle et l'acide chloracetique-[1-14C]. L'acylation de l'[(amino-4Expand


Potential probe for isolation of the β-adrenoceptor, chloropractolol
A TECHNIQUE which has proved highly successful in the isolation and identification of pharmacological receptors, is the use of a high affinity, selective label which binds irreversibly to theExpand
Comparative chronotropic activity of β‐adrenoceptive antagonists
1 . Chronotropic dose‐response curves (non‐cumulative) for β‐adrenoceptive antagonists were constructed from results in rats anaesthetized with pentobarbitone and depleted of catecholamines byExpand
Fluorometric and radiometric assays for propranolol were developed in order to determine whether the antagonist is measurably taken up by isoproterenol receptors in cardiac tissue. The equilibriumExpand
A theory of drug action based on the rate of drug-receptor combination
  • W. Paton
  • Chemistry
  • Proceedings of the Royal Society of London. Series B. Biological Sciences
  • 1961
A theory of drug action is developed on the assumption that excitation by a stimulant drug is proportional to the rate of drug-receptor combination, rather than to the proportion of receptorsExpand
  • H. Schild
  • Biology, Medicine
  • British journal of pharmacology
  • 1975
Two expressions for calculating receptor occupancy by antagonist in competitive drug antagonism are contrasted.