Effect of gabapentin derivates on mechanical allodynia-like behaviour in a rat model of chronic sciatic constriction injury.
A series of mutual prodrugs derived from gabapentin, pregabalin, memantine, venlafaxine were synthesized and their pharmacological properties to treat neuropathic pain were investigated in a rat model of chronic sciatic nerve constriction injury (CCI). In vivo evaluation demonstrated that the mutual prodrugs 2002413A, 2002823A composed of two gabapentins, 2002414 composed of gabapentin and pregabalin were effective in reversal tactile allodynia in CCI rats. The prodrugs 2002413A, 2002414 had no significant influence on the rotarod activity. The result suggest that the prodrugs may be possible candidates for further development.
Hong-Ju
Yang
Y
Beijing Institute of Pharmacology and Toxicology, Pharmacology Department, Taiping Road 27, Beijing 100850, China. yanghongju618@sina.com
He
Liu
L
Wei-Guo
Shi
S
Nan
Zhao
Z
Wei-Xiu
Yuan
Y
Zhong-Wei
Jiang
J
Jun-Wei
Wang
W
Zheng-Hua
Gong
G
Bo-Hua
Zhong
Z
Zhi-Pu
Luo
L
Zhe-Hui
Gong
G
D000588:Amines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D002908:Chronic Disease; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D004195:Disease Models, Animal; D000077206:Gabapentin; D008559:Memantine / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects; D000069583:Pregabalin; D011355:Prodrugs / Q000138:chemical synthesis; D051381:Rats; D020426:Sciatic Neuropathy / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D000069470:Venlafaxine Hydrochloride; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*
D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D003511:Cyclohexanols; D011355:Prodrugs; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000069470:Venlafaxine Hydrochloride; D008559:Memantine