Differential neuropsychopharmacological influences of naturally occurring tropane alkaloids anisodamine versus scopolamine.
Two naturally occurring tropane alkaloids, anisodamine and scopolamine, structurally dissimilar in one OH group, are well established as muscarinic acetylcholine receptor (mAChR) antagonists in clinic and basic research. However, experimental evidence for central effects of anisodamine is limited and conflicting compared with that of scopolamine. In the present study, Morris water maze test, long-term potentiation (LTP) recording and receptor radioligand binding assays were used to explore the disparity in neuropsychopharmacological influences of anisodamine versus scopolamine and possible mechanisms. Anisodamine, at 10-40-fold higher doses than those of scopolamine, did not produce any spatial cognitive deficits as scopolamine, but tended to improve cognition at the repeated high doses. LTP in vivo was then adopted to predict BBB permeability of the muscarinic antagonists following systemic drug administration. Contrary to scopolamine, anisodamine did not influence the formation of LTP in the CA(1) region of rat hippocampus at 40-fold higher dose than that of scopolamine. Additionally, receptor radioligand binding assays (RRLBA) revealed that the binding affinity of anisodamine to mice brain mAChR was much lower than that of scopolamine. The findings suggested that anisodamine did not impair cognition nor depress LTP primarily due to its poor BBB permeability. This work enlarged knowledge of structure-activity relationship among tropane alkaloids, meanwhile providing evidence for more reasonable drug prescription in clinic.
Zhang
Wei-Wei
WW
Department of Pharmacy, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Song
Ming-Ke
MK
Cui
Yong-Yao
YY
Wang
Hao
H
Zhu
Liang
L
Niu
Yin-Yao
YY
Yang
Li-Min
LM
Lu
Yang
Y
Chen
Hong-Zhuan
HZ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009480:Neuropharmacology; D011600:Psychopharmacology; D011897:Random Allocation; D011930:Reaction Time / Q000187:drug effects; D012601:Scopolamine / Q000737:chemistry / Q000494:pharmacology*; D012991:Solanaceous Alkaloids / Q000737:chemistry / Q000494:pharmacology*
D016166:Free Radical Scavengers; D012991:Solanaceous Alkaloids; C003922:anisodamine; D012601:Scopolamine