Effects of huperzine A and B on skeletal muscle and electro¬encephalogram

Both huperzine A and B (Hup-A and B) are new alkaloids isolated from Chinese herb Huperzio serrata. We have demonstrated that Hup-A and B are reversible ChE inhibitors exhibiting selective inhibition on AChE, This paper presents evidences that Hup-A and B potentiated the muscle contraction and caused EEG activation, In rat’s isolated phrenic nerve-diaphragm preparation, Hup-A, B, neostigmine (Neos)，physostigmine (Phys) and galanthamine (Gal) were examined in molar concentrations, 0.35μmol/L Hup-A or 2.24μmol/L Hup-B increased the amplitude of muscle contraction in 10 min by 19 and 21%, while at a concentration of 0.5μmol/L and 9.5μmol/L the increases were 70 and 81%, respectively. There were good concentration-response relationships. The order of potentiative activity was Phys>Neos>Hup-A>Gal>Hup-B. In the isolated and chronically denervated hemi-diaphragmmuscles of the rats, Ach 0.15 μmol/L and Neos 20μmol/L produced reversible contractures, but Hup-A and B (100μmol/L) did not. By using anesthetized rat’s sciatic-tibialis preparation, the order of potentiative action in muscle contraction was Neos>Hup-A>Phys>Hup-B>Gal after iv administration, conversely, the potentiative activity of Hup-A was more potent than that of Neos when administration ig. The anti-curare activity was Neos>Hup-A>Phys>Hup-B>Gal. Salivation of mice was graded visually (0,1,2,3 and 4). Dose-response cureves for salivation indicated that both Hup-A and B were less potent than that of Neos and Phys. In experiments performed on unaesthetic rabbitze dwith intact brains, Hup-A 0.05 mg/kg produced alert EEG pattern which started within 6.6±1.4 min after iv and lasted 11±8 min, atropine 2 mg/kg antagonized this effect but MA did not. The same effect was also observed with Hup-B at the dose of 0.5 mg/kg, but its action duration (37±1 min) was longer than that of Hup-A. The order of therapeutic index was Hup-B>Hup-A>Neos>Phys in mice and was Hup-B >Hup-A>Gal>Neos>Phys in rats. These results indicate that Hup-A and B should be of therapeutic value for treatment some disease concerning with functional deficiency of peripheral and central cholinergic system.