PROKINETIC AGENTS FOR TREATING GASTRIC HYPOMOTILITY AND RELATED DISORDERS

摘要

Stasis is treated or prevented in all or any part or parts of the stomach of a patient, especially a human patient, in need of such treatment, where said stasis results from hypomotility in the stomach, particularly gastric hypomotility with delayed emptying of the liquid and/or solid contents of the stomach. Gastric or gastrointestinal disorders are also treated which are characterized by one or more symptoms selected from pain, nausea, vomiting, heartburn, postprandial discomfort, indigestion and gastroesophageal reflux. Such treatment or prevention is achieved by administering to the patient a therapeutically effective amount of an inhibitor of phosphodiesterase-4 (PDE4), including isozyme subtypes thereof, sufficient to treat or prevent such hypomotility or gastric or gastrointestinal disorder in said patient. The PDE4 inhibitor comprises a compound of Formula (IA) or (IB): chemistry chemdraw filechemistry mol file;where in a preferred embodiment, R is cyclopentyl or cyclohexyl; R¹ is (C₁-C₂) alkyl; one of R²_a and R²_b is hydrogen and the other is a substituent of partial Formula (1.0.0) above, where the dashed line represents a single bond, m is 0, R¹¹³ and R¹¹⁴ are in a cis relationship to each other, R¹¹³ is cyano, R¹¹⁵ is hydrogen, and R¹¹⁴ is carboxy, —CH₂OH, or —CH₂C(═O)NH₂. ;Pharmaceutical compositions are also described which are useful for carrying out the above-mentioned methods of treatment and prevention, and which are also useful in the treatment of a gastric or gastrointestinal disorder in a patient which comprises with respect to said patient, (i) a sign or concomitant of diabetic neuropathy, anorexia nervosa, achlorhydria, gastrointestinal surgery, post-surgical recovery in the period of emergence from general anesthesia; or the administration of morphine and morphine-like opioids; (ii) a secondary aspect of a primary disease or disorder in said patient which is organic, wherein said disease or disorder involves particularly a gastroenteric or gastroesophageal organ or tissue, or an organ or tissue of the central nervous system of said patient; or (iii) an adverse side effect of a different therapeutic agent administered to said patient in the course of treating another unrelated disease or disorder in said patient.