Reproduction and Development Toxicity of Anti-Alzheimer′s Drug Dehydroevodiamine-HCl

치매 치료제 염산 디히드로에보다이아민의 생식 및 발생 독성

  • Published : 2002.12.01

Abstract

Dehydroevodiamine-HCl (DHED), which is a component separated from Evodia rutaecarpa Bentham, has novel anticholinesterase and antiamnesic activities in a scopolamine-induced amnesia model. Several studies suggest that DHED might be an effective drug for Alzheimer's disease and a vascular type of dementia. DHED was at dose levels of 0, 50, 100 and 200 mg/kg/day administered intraperitoneally to Sprague-Dawley male rats for 60 days before mating and to females from 14 days before mating to 7 days after mating. Effects of the DHED on general symptom and reproductive performance of parent animals and embryonic development were examined. In male parents, whereas no death was observed, reduction in the increase rate of body weight was found at 200 mg/kg. In female parents, both of the mating performance and the fertility of parent animals were decreased at 200 mg/kg, but not significantly. In 200 mg/kg treated group, the fetal death rate was increased but total fetuses showed no changes compared to the control group. There were no malformed F1 fetuses in all groups.

Keywords

References

  1. Whitehouse, P. J., Price, D. L., Struble, R. G., Clark, R. W., Coyle, J. T. and DeLong, M. R. : Alzheimer's disease and senile dementia:loss of neurons in the basal forebrain. Science. 215, 1237 (1982)
  2. Marx, J. L. : Alzheimer's drug trial put on hold. Science. 238, 1041 (1987) https://doi.org/10.1126/science.3317822
  3. Rogers, R. L., Meyer, J. S., Mortel, K. F., Mahurin, R.K. and Judd, B. W. : Decreased cerebral blood flow preceds multiinfact dementia, but follows senile dementia of Alzheimer type. Neurology. 36, 1 (1986)
  4. Ni, J. W., Ohta, H., Matsumoto, K. and Watanabe, H. : Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Res. 653, 231 (1994) https://doi.org/10.1016/0006-8993(94)90394-8
  5. Yonemori, F., Yamada, H., Yamaguchi, T., Uemura, A. and Tamura, A. : Spatial memory disturbance after focal cerebral ischemia in rats. J. Cereb, Blood Flow Metab. 16, 973 (1996)
  6. Yang, H. Y., Li, S. Y. and Chen, C. F. : Hypotensive effects of dehydroevodiamine,a quinazolinocarboline alkaloid isolated from Evodia rutaecarpa. Asia Pac. J. Pharmacol. 3, 191 (1998)
  7. Haji, A., Momose, Y., Takeda, R., Nakanishi, S., Horiuchi, T. and Arisawa, M. : Increased feline cerebral blood flow induced by dehydroevodiamine hydrochloride from Evodia rutaecarpa. J. Nat. Prod. 57, 387 (1994) https://doi.org/10.1021/np50105a009
  8. Loh, S. H., Lee, A. R., Huang, W. H. and Lin, C. I. : Ionic mechanisms responsible for the antiarrhythmic action of dehydroevodiamine in guinea-pig isloated cardiomyocytes. Br. J. Pharmacol. 106, 517 (1992)
  9. Park, C. H., Lee, Y. J., Lee, S. H., Choi, S. H., Kim, H. S., Jeong, S. J., Kim, S. S. and Suh, Y. H. : Dehydroevodiamine-HCI prevents impairment of learning and memory and neuronal loss in rat models of cognitive disturbance. J. Neurochem. 74, 244(2000) https://doi.org/10.1046/j.1471-4159.2000.0740244.x