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.
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.
Mikus
E G
EG
Laboratory for Respiratory Pharmacology of Research & Development Directorate, Chinoin Pharmaceutical and Chemical Works Co., Ltd., Budapest, Hungary.
Kapui
Z
Z
Korbonits
D
D
Boér
K
K
Boronkay
E
E
Gyürky
J
J
Révész
J
J
Lacheretz
F
F
Pascal
M
M
Arányi
P
P
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology*
D000996:Antitussive Agents; D001993:Bronchodilator Agents; D006633:Histamine Antagonists; D010069:Oxadiazoles; D011687:Purines; D018047:Receptors, Purinergic P1; D013806:Theophylline; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; C106302:1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7-((5-methyl-1,2,4-oxadiazol-3-yl)methyl)-