Development of a multiaction beta blocker. Scientific challenges and regulatory needs.
The search for the ideal antihypertensive drug is ongoing. Since hypertension initially is a relatively symptom-free disease, it is important that any agent developed be not only efficacious but also safe, with minimal side effects. Additionally such a drug should ideally possess both primary and secondary cardiovascular preventive properties. This review discusses the most commonly used antihypertensive drugs in the light of these goals, and highlights the development of multiaction drugs. Carvedilol, which is a nonselective beta-blocking and alpha 1-blocking drug, with additional Ca(2+)-antagonistic properties, is being developed as an antihypertensive, antianginal drug and as an adjunct therapy in congestive heart failure. The development challenges for this single-entity drug are discussed and evidence for its antihypertensive efficacy, as well as its antianginal efficacy, is presented. The cardioprotective potential of carvedilol based on preclinical experiments is addressed. Finally, the regulatory questions regarding the development of a multiaction drug are highlighted.
Lessem
J N
JN
SmithKline Beecham, King of Prussia, PA 19406.
Lukas
M A
MA
D000319:Adrenergic beta-Antagonists; D000787:Angina Pectoris / Q000188:drug therapy; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D002227:Carbazoles; D000077261:Carvedilol; D017277:Drug Approval; D016166:Free Radical Scavengers; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D011412:Propanolamines; D014665:Vasodilator Agents
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D002227:Carbazoles; D016166:Free Radical Scavengers; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol