Effect of cholinesterase inhibition in vitro by huperzine analogs

Huperzine (Hup) A and B were first discovered and studied by Chinese. Fourteen analogs of Hup were tested for their anticholinesterase (anti-ChE) activity by colorimetric method using rat erythrocyte membrane and serum as enzyme sources. Hup-A showed the highest anti-AChE potency. The anti-BuChE activity of (-)dihydro and (-)tetrahydro analogs were potent than those of Hup-A. Their anti-AChE activities were comparable to those of physostigmine and galanthamine. Dihydro analog inhibition was of the mixed competitive type with a Ki value of 0.12 mumol.L-1. Tetrahydro analog inhibition was of the competitive type with a Ki value of 0.56 mumol.L-1. They were different from isoflurophate to bond to AChE in a reversible manner.