Methods of treating pulmonary disease using acetazolamide and structurally related derivatives
Introduction Alveolar hypoxia, as occurs with chronic lung diseases or ascent to high altitude, results in hypoxic pulmonary vasoconstriction (HPV). Exaggerated HPV causes high altitude pulmonary edema(HAPE) and may complicate the course of patients with chronic cardiopulmonary disease. HPV is believed to require Ca influx into pulmonary arterial smooth muscle cells. The oral carbonic anhydrase (CA) inhibitor acetazolamide (AZ) is frequently used for prevention and treatment of acute mountain sickness in humans and to prevent 2+
HPV and HAPE in animals. Researchers at the University of Washington have identified that the mechanism by which AZ inhibits hypoxiainduced Ca 2+
responses is independent of CA inhibition and propose new methods and compounds for treating pulmonary hypertensive disorders that will be free of the side effects associated with chronic CA inhibition. Technology description This invention provides the composition of structurally related derivatives of AZ for which one of the amine hydrogens of the sulfonamide moiety has been replaced with a methyl group, abolishing their CA-inhibiting activity. This invention also includes an inhalable composition comprising AZ or AZ derivatives and an inhalable carrier. Business opportunity The expected benefits of this invention include a new oral and inhaled medication for the treatment of pulmonary hypertension. Several forms of pulmonary hypertension (PH) are anticipated to be effectively treated including primary or idiopathic pulmonary hypertension, PH secondary to chronic lung diseases, short and long term high altitude residence, sleep apnea syndrome, atrial septal defects with left to right shunting, and PH associated with other conditions such as chronic liver disease, anorexigenic drugs, and HIV. Intellectual property position The University has applied for patent protection to secure the rights to this technology. Publications Am J Physiol Lung Cell Mol Physiol. 2007 Jan; [Epub ahead of print]
Am J Physiol Lung Cell Mol Physiol. 2007 Aug 292:L178-84.
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