(-)-Clausenamide potentiates synaptic transmission in the dentate gyrus of rats.
The effect of clausenamide on synaptic transmission in the dentate gyrus of rats in vivo and its possible mechanism of action were investigated in this study. Four of 16 enantiomers showed potentiating effects on basal synaptic transmission in anesthetized animals. By comparing one pair of enantiomers, (-)-clausenamide and (+)-clausenamide, we can report three primary findings: (1) (-)-clausenamide potentiated synaptic transmission in both anesthetized and freely moving animals while (+)-clausenamide showed no or little effect; (2) (-)-clausenamide increased the magnitude of long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in anesthetized animals whereas (+)-clausenamide had no effect; (3) voltage-dependent calcium channels (VDCCs) calcineurin and calpain are involved in (-)-clausenamide-induced potentiation of synaptic transmission. Because hippocampal LTP is thought to reflect a cellular mechanism involved in learning and memory, our findings may provide the pharmacological basis for understanding the nootropic mechanisms of (-)-clausenamide, which is the first chiral nootropic agent developed in China.
Xu
Lin
L
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Liu
Shao-Lin
SL
Zhang
Jun-Tian
JT
D000818:Animals; D019703:Calcineurin / Q000737:chemistry / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry; D002154:Calpain / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects*; D016503:Drug Delivery Systems; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects; D007769:Lactams / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008956:Models, Chemical; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D015220:Calcium Channels; D004365:Drugs, Chinese Herbal; D007769:Lactams; D017705:Lignans; C053048:clausenamide; D019703:Calcineurin; D002154:Calpain