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Arzneimittelforschung 2003; 53(6): 393-401
DOI: 10.1055/s-0031-1297126
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

General Pharmacology of Indole [2′,3′:3,4]pyrido[2,1-b]quinazolinium-5,7,8,13-tetrahydro-14-methyl-5-oxochloride, a New Anti-dementia Agent

Cheol Hyoung Park
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Se Hoon Choi
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Chan-Hyung Kim
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Ji-Heui Seo
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Ja Wook Koo
b   School of Biological Sciences, College of Natural Scienceb, Seoul National University, Seoul, Korea
,
Jong-Cheol Rah
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Hye-Sun Kim
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Sung-Jin Jeong
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Wan-Seok Joo
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Young-Jae Lee
c   Department of Veterinary Medicine, Cheju National University, Cheju, Korea
,
Yong Sik Kim
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Myung-Suk Kim
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
,
Yoo-Hun Suh
a   Department of Pharmacology, College of Medicine, National Creative Research Initiative Centre for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, Korea
› Author Affiliations
Further Information

Publication History

Publication Date:
25 December 2011 (online)

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Summary

The general pharmacological properties of indolo[2’,3’:3,4]pyrido[2,1-b]quinazolinium-5,7,8,13-tetrahydro-14-methyl-5-oxo-chloride (dehydroevodiamine-HCl, DHED, CAS 67909-49-3), a new potential anti-dementia agent, were studied to investigate side effects using various experimental animals. Both oral and intraperitoneal administration of DHED had no effects on the central nervous system except that they showed an analgesic activity. DHED had no significant effect on heart rate, blood pressure and coronary flow in isolated rat hearts. DHED had negligible effects on the autonomic nervous system and smooth muscle in isolated rat ileum, rat vas deferens and rat aorta. DHED did not influence the gastrointestinal system except that it inhibited the intestinal travel of a charcoal meal in mice. Neither blood coagulation mechanism nor liver function was affected by DHED.

Therefore, it is concluded from these general pharmacological studies that DHED does not induce any serious side effects at the dose levels showing anticholinesterase and memory enhancing activities in the experimental animals.

Zusammenfassung

Allgemeine Pharmakologie der neuen Antidemenz-Wirksubstanz Indol[2’,3’:3,4] pyrido[2,1-b]quinazolinium-5,7,8,13-tetrahydro-14-methyl-5-oxo-chlorid

Die allgemeinen pharmakologischen Eigenschaften von Indol[2’,3’:3,4] pyrido[2,1-b]quinazolinium-5,7,8,13-tetrahydro-14-methyl-5-oxo-chlorid (Dehydroevodiamin-HCL, DHED, CAS

67909-49-3), einer neuen potentiellen Antidemenz-Wirksubstanz, wurden an verschiedenen Tierarten untersucht, um Aufschluß über die Nebenwirkungen zu erhalten. Sowohl bei oraler als auch bei intraperitonealer Verabreichung zeigte DHED keine Wirkungen auf das Zentral-nervensystem mit Ausnahme einer analgetischen Aktivität. DHED hatte an isolierten Rattenherzen keine signifikante Wirkung auf Herzfrequenz, Blutdruck und koronare Durchblutung. Am isolierten Ileum und Vas deferens sowie an der isolierten Aorta von Ratten zeigte DHED eine vernachlässigbare Wirkung auf das autonome Nervensystem und die glatte Muskulatur. DHED bewirkte keine Veränderung des gastrointestinalen Systems mit Ausnahme einer Hemmung des intestinalen Transports von Kohle-Nahrung bei Mäusen. Weder der Blutgerinnungsmechanismus noch die Leberfunktion wurde von DHED beeinflußt.

Aus diesen allgemein-pharmakologischen Untersuchungen kann geschlossen werden, daß DHED in den Dosierungen, mit denen eine Cholinesterase-hemmende Aktivität und eine Verbesserung der Gedächtnisleistung erzielt wird, bei Versuchstieren keine ernsten Nebenwirkungen hervorruft.

Key words

Anti-dementia agent - CAS 67909-49-3 - Evodia rutaecarpa - Indole[2’,3’:3,4]pyrido[2,1-b] quinazolinium-5,7,8,13 - -tetrahydro-14-methyl-5-oxo-chloride, general pharmacology, mouse, rabbit, rat