Atenolol Tenormin

Structural Formula

Ball-and-Stick Model

Structural Formula

= Carbon = Hydrogen M = Oxygen = Nitrogen

Year of discovery of the first beta blocker (ß-blocker): 1958; Year it entered the market: 1976 (AstraZeneca); Drug category: ß-blocker - a substance that affects the heart and the circulatory system (veins and arteries) by slowing the heart rate and relaxing the blood vessels. Main uses: To lower blood pressure, lower heart rate, reduce chest pain (angina), reduce risk of or attenuate heart attack. Approximate number of people treated annually: Over 20 million; Related drugs: Propranolol, Practolol, Nadolol, Oxprenolol, Penbutolol, Betaxolol, Metoprolol, Nebivolol, Carvedilol, Labetalol. Timolol (for glaucoma).

Hypertension, also known as high blood pressure, is a clinical condition in which the arterial blood pressure at rest exceeds on average 130/90 mm Hg. If left untreated, this condition promotes impaired circulation and cardiovascular disease, which can lead to heart attack or stroke. The incidence of hypertension increases with excess weight, age and family history of the disease. Statistics show that by 2005 more than 65 million people in the US had hypertension.

In the 1950s James Black, a British pharmacologist, and a team of chemists studied the possibility that molecules which could block the binding of (3-adrenergic amines (e.g., adrenaline) to the |3-adrenergic receptor might reduce blood pressure. This work led to the first successful antihypertensive P-blocker (and the 1988 Nobel Prize in Medicine).

The usual approach to drug discovery before the 1960s was to synthesize a large number of compounds and test them on animals. With Black's work and the growing knowledge of the biochemical basis of a given medical condition, the design of drugs became more rational. The development of P-blockers is an early example of this involving two important catecholamine hormones, adrenaline and noradrenaline (see structures on the right). The stimulation of the sympathetic nervous system (e.g., by fear) results in the increase of the adrenaline level that in turn increases blood pressure. Adrenaline and noradrenaline act by binding to the ubiquitous adrenergic receptors (adrenoceptors) of two types, a and p. Upon binding, the heart is stimulated while the blood vessels are constricted (this is the so-called fight or flight response).

Adrenaline

Noradrenaline

Adrenaline

Noradrenaline

Atenolol is a compound that binds competitively to the p-adrenoceptor and blocks the action of adrenalin (thus the name p-blocker). This action slows the heart and lowers blood pressure. For patients with angina or congestive heart failure, atenolol is especially beneficial, since it reduces the oxygen demand of the heart muscle. However, p-blockers are contraindicated for asthmatics because they cause broncho-constriction, whereas bronchodilating p-agonists are beneficial (see salmeterol, a p-agonist on page 50).1

The family of P-blocker compounds has been so successful that many major pharmaceutical companies have developed their own versions. Currently there are about 20 p-blocker drugs on the market.2,3

1. Curr. Pharm. Des. 2007, 13. 229-239; 2. Curr. Hypertens. Rep. 2006, 8, 279-286; 3. Curr. Hypertens. Rev. 2007 3, 1520; Refs. p. 83

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