Experimental studies on the antitussive properties of the new xanthine derivative 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]. 2nd communication: investigations on theophylline-like activities

• Published in: Arzneimittel-Forschung Vol. 47; no. 12; p. 1358
• Main Authors: Mikus, E G, Kapui, Z, Korbonits, D, Boér, K, Boronkay, E, Gyürky, J, Révész, J, Lacheretz, F, Pascal, M, Arányi, P
• Format: Journal Article
• Language: English
• Published: Germany 01.12.1997
• Subjects: 2',3'-Cyclic-Nucleotide Phosphodiesterases - metabolism; Animals; Antitussive Agents - pharmacology; Autonomic Nervous System - drug effects; Autonomic Nervous System - physiology; Bronchodilator Agents - pharmacology; Electrophysiology; Female; Guinea Pigs; Hemodynamics - drug effects; Histamine Antagonists - pharmacology; In Vitro Techniques; Male; Oxadiazoles - pharmacology; Purines - pharmacology; Rats; Rats, Wistar; Receptors, Purinergic P1 - drug effects; Respiratory Mechanics - drug effects; Theophylline - pharmacology
• ISSN: 0004-4172

CH-13584 (formerly: KHL-8425, 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl], CAS 115779-20-9) is a new xanthine derivative, structurally related to theophylline. Potent antitussive activity in the 4 to 8 mg/kg dose range, by the oral route, was already demonstrated for this compound. In the present work, it is shown that contrary to theophylline, CH-13584 does not interact with adenosine A1 receptor and is a weaker inhibitor of cyclic nucleotide phosphodiesterase. In addition, CH-13584 is a less active bronchodilator in vitro and in vivo. It is also devoid of the cardiovascular and behaviour side-effects of theophylline and of effects on diuresis at dosage well above the antitussive dose. CH-13584, therefore, has a different pharmacological profile compared to theophylline and is devoid of the known side-effects of the latter. Such differences could result from a different biochemical profile.