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

Zoltán Kapui, Endre Gustáv Mikus, Judit Bence, Katalin Gerber, Klinga Boér, Dezsõ Korbonits, A. Borsodi, Péter Arányi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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. ow intracerebroventricular (i.c.v.) naloxone, i.m. nor-binaltorphimine or s.c. β-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.

Original languageEnglish
Pages (from-to)1147-1155
Number of pages9
JournalArzneimittel-Forschung
Volume48
Issue number12
Publication statusPublished - 1998

Fingerprint

Antitussive Agents
Xanthine
Opioid Analgesics
Substance-Related Disorders
Communication
Derivatives
Pharmaceutical Preparations
Naloxone
Diprenorphine
Codeine
kappa Opioid Receptor
delta Opioid Receptor
3,7-dihydro-3-methyl-7-((5-methyl-1,2,4-oxadiazol-3-yl)methyl)-1H-purine-2,6-dione
Cough
Citric Acid
Morphine
Rats
Injections

Keywords

  • 1H-Purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]
  • Antitussives
  • CAS 115779-20-9
  • CH-13584, drug dependence studies, opioid mechanisms
  • Codeine
  • Dextromethorphan
  • Morphine
  • Naloxone

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Pharmacology

Cite this

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. / Kapui, Zoltán; Mikus, Endre Gustáv; Bence, Judit; Gerber, Katalin; Boér, Klinga; Korbonits, Dezsõ; Borsodi, A.; Arányi, Péter.

In: Arzneimittel-Forschung, Vol. 48, No. 12, 1998, p. 1147-1155.

Research output: Contribution to journalArticle

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