Chemical Properties
White or almost white powder.
Originator
Tenormin,Stuart,UK,1976
Definition
ChEBI: An ethanolamine compound having a (4-carbamoylmethylphenoxy)methyl group at the 1-position and an N-isopropyl substituent.
Manufacturing Process
1 gram of 1-p-carbamoylmethylphenoxy-2,3-epoxypropane and 10 ml of
isopropylamine in 25 ml of methanol is heated in a sealed tube at 110°C for
12 hours. The mixture is evaporated to dryness and the residue is partitioned
between 50 ml of chloroform and 50 ml of aqueous 2 N hydrochloric acid. The
aqueous acidic layer is separated, made alkaline with sodium carbonate and
extracted twice with 50 ml of chloroform each time. The combined extracts
are dried and evaporated to dryness and the residue is crystallized from ethyl
acetate. There is thus obtained 1-p-carbamoylmethyiphenoxy-3-
isopropylamino-2-propanol, MP 146-148°C.
The 1-p-carbamoylmethylphenoxy-2,3-epoxypropane used as starting material
may be obtained as follows: a mixture of 3.2 grams of phydroxyphenylacetamide,
25 ml of epichlorohydrin and 6 drops of piperidine is
heated at 95-100°C for 6 hours. The mixture is cooled and filtered and the
solid product is crystallized from methanol. There is thus obtained 1-pcarbamoylmethylphencxy-
2,3-epoxypropane, MP 158-160°C.
Brand name
Tenormin (AstraZeneca).
Therapeutic Function
Beta-adrenergic blocker
General Description
Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards
Biological Activity
Cardioselective β -adrenergic blocker. Antihypertensive, antianginal, antiarrhythmic.
Biochem/physiol Actions
Selective β1-adrenoceptor antagonist; antihypertensive; antianginal; antiarrhythmic.
Clinical Use
Beta-adrenoceptor blocker:
Hypertension
Angina
Arrhythmias
Veterinary Drugs and Treatments
Atenolol may be useful in the treatment of supraventricular tachyarrhythmias,
premature ventricular contractions (PVC’s, VPC’s),
systemic hypertension and in treating cats with hypertrophic cardiomyopathy.
Atenolol is relatively safe to use in animals with bronchospastic
disease.
in vitro
(r,s)-atenolol was found to differ slightly regarding potency and to be practically equal regarding relative selectivity, while ici 141,292 had slightly higher relative selectivity and much higher potency. (r,s)-atenolol exhibited highest affinity for the beta 1-receptor population. in contrast, ici 118,551 exhibited a very high relative selectivity with highest affinity for the beta 2-receptor subtype [1].
in vivo
the renal effects of (r,s)-atenolol in rats were studied. results showed that the iv infusion of (r,s)-atenolol increased urinary sodium excretion, urine volume (uv), urinary potassium excretion and urinary chloride excretion. (r,s)-atenolo intraaortally injected produced an increase in uv and sodium concentration in the urine, inducing a more marked increase in total sodium amount excreted from both kidneys [2].
Drug interactions
Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Analgesics: NSAIDs antagonise hypotensive effect.
Anti-arrhythmics: increased risk of myocardial
depression and bradycardia; increased risk of
bradycardia, myocardial depression and AV block
with amiodarone; increased risk of myocardial
depression and bradycardia with flecainide.
Antidepressants: enhanced hypotensive effect with
MAOIs.
Antihypertensives: enhanced hypotensive effect;
increased risk of withdrawal hypertension with
clonidine; increased risk of first dose hypotensive
effect with post-synaptic alpha-blockers such as
prazosin.
Antimalarials: increased risk of bradycardia with
mefloquine.
Antipsychotics enhanced hypotensive effect with
phenothiazines.
Calcium-channel blockers: increased risk of
bradycardia and AV block with diltiazem;
hypotension and heart failure possible with
nifedipine and nisoldipine; asystole, severe
hypotension and heart failure with verapamil.
Cytotoxics: possible increased risk of bradycardia
with crizotinib.
Diuretics: enhanced hypotensive effect.
Fingolimod: possibly increased risk of bradycardia.
Moxisylyte: possible severe postural hypotension.
Sympathomimetics: severe hypertension with
adrenaline and noradrenaline and possibly with
dobutamine.
Metabolism
Roughly half of an orally administered dose of
atenolol (Tenormin) is absorbed.The drug is eliminated
primarily by the kidney and unlike propranolol, undergoes
little hepatic metabolism. Its plasma half-life is approximately
6 hours, although if it is administered to a
patient with impaired renal function, its half-life can be
considerably prolonged.
References
[1] golf, s. ,bjornerheim, r.,erichsen, a., et al. relative selectivity of different β-adrenoceptor antagonists for human heart β1- and β2-receptor subtypes assayed by a radioligand binding technique. scandinavian journal of clinical and laboratory investigation 47(7), 719-723 (1987).
[2] yamazaki n, monma y, tanabe t. effects of propranolol and atenolol on the rat kidney. nihon yakurigaku zasshi. 1983 may;81(5):333-42.
[3] stoschitzky k, egginger g, zernig g, klein w, lindner w. stereoselective features of (r)- and (s)-atenolol: clinical pharmacological, pharmacokinetic, and radioligand binding studies. chirality. 1993;5(1):15-9.
