Abstract: OBJECTIVE To synthesize bivalent γ-carboline derivatives and determine their acetylcholinesterase inhibition activity. METHODS The key intermediate γ-carboline was synthesized by Fischer method using N-acetyl- 3-bromo-4-piperidone and phenylhydrazine as starting materials. The γ-carboline synthesized was then reacted with ω,ω’- dibromoalkanes in the presence of NaH to form bivalent γ-carboline derivatives. Methylation of γ-carboline derivative with iodomethane in methanol yielded its quaternary ammonium salt. The acetylcholinesterase activity was measured by Ellman method with slight modification. RESULTS Seven novel carboline derivatives were synthesized and their structures were characterized by IR, ¹H-NMR, ¹³C-NMR and ESI-MS. The results of pharmacological experiments indicated that all the target compounds showed inhibition activity against the acetylcholinesterase. Compound 4g exhibited inhibitory activity similar to that of the positive control donepezil. CONCLUSION Bivalent γ-carboline derivatives have inhibition activity against the acetylcholinesterase. The length of the connecting chain has an impact on the activity. It shows the best activity with chain length of eight carbon atoms, and the quaternization of tertiary nitrogen in the structure is beneficial for raising the inhibitory activity.