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]. 3rd communication: examinations on opioid mechanisms and physical drug dependence.
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) showed antitussive effect on the citric acid spray-induced cough model. The antitussive effect of p.o. CH-13584 was antagonised by i.m. or intracerebroventricular (i.c.v.) naloxone, i.m. nor-binaltorphimine or s.c. beta-funaltrexamine. Intracerebroventricular administration of CH-13584 induced long-lasting antitussive effect which was antagonised by coadministration of i.c.v. naloxone. CH-13584 did not bind to opioid mu, delta, kappa receptor in vitro or inhibit the [3H]diprenorphine binding in vivo. Two-week treatment with CH-13584 up to the dose of 100 mg/kg p.o. did not produce autonomic and behavioural signs of withdrawal induced either by drug withdrawal or by naloxone injection, while morphine and codeine induced characteristic opioid-type physical dependence in rats.
Kapui
Z
Z
Chinoin Pharmaceutical and Chemical Works Co., Ltd., Budapest, Hungary.
Mikus
E G
EG
Bence
J
J
Gerber
K
K
Boér
K
K
Korbonits
D
D
Borsodi
A
A
Arányi
P
P
D000818:Animals; D000996:Antitussive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control; D006168:Guinea Pigs; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D010069:Oxadiazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D011687:Purines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders / Q000503:physiopathology*
D000996:Antitussive Agents; D009292:Narcotic Antagonists; D010069:Oxadiazoles; D011687:Purines; D011957:Receptors, Opioid; C106302:1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7-((5-methyl-1,2,4-oxadiazol-3-yl)methyl)-