In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine ( TMP) /chalcone hybrids ( 2-26) were synthesized and evaluated based on the principle of bioisostere and hybrid-ization. They exerted inhibitory activity against adenosine diphosphate ( ADP )-induced and arachidonic acid ( AA)-induced platelet aggregation to varied extent. Among them, compound 8 was the most potent with IC50 of 0. 14 mmol/L on ADP-induced platelet aggregation ( 9. 1 folds of TMP and 10. 5 folds of chalcone ) and 0. 09 mmol/L on AA-induced platelet aggregation ( 8. 8 folds of TMP and 10. 0 folds of chalcone) , which was superior to clinically used anti-platelet drug aspirin ( ASP, IC50 =0. 15 mmol/L) .

Objective:To evaluate the effect of different doses of cisatracurium on the monitoring of motor-evoked potentials (MEPs) in the patients undergoing intracranial aneurysm clipping.Methods:Eighty patients of both sexes, aged 18-64 yr, with body mass index <30 kg/m 2, of American Society of Anesthesiologists physical statusⅠor Ⅱ, with Hunt-Hess grade 0-Ⅱ, undergoing intracranial aneurysm clipping under general anesthesia, were divided into 4 groups ( n=20 each) using a random number table method: conventional group (group R) and different doses of cis-atracurium groups (Cis 1-3 groups). After anesthesia induction, muscle relaxation was monitored, and train-of-four (TOF) stimulation (frequency 2 Hz, wave width 0.2 ms, interval 15 s) was applied to the ulnar nerve of forearm, and the TOF ratio was recorded as the baseline value (T 1). MEPs were assessed with a nerve electrophysiology monitor after induction of anesthesia.In Cis 1-3 groups, cis-atracurium 0.625, 0.833 and 1.000 μg·kg -1·min -1 were intravenously infused, while the equal volume of normal saline was given instead in group R when TOF ratio returned to the baseline value and MEPs could be effectively elicited.At T 1, immediately after dural incision (T 2), immediately after aneurysm occlusion (T 3) and immediately after dural closure (T 4), the TOF ratio, effective elicitation of intraoperative MEPs, and occurrence of intraoperative cardiovascular events, recovery of spontaneous breathing and body movement were recorded. Results:Compared with group R, no significant change was found in TOF ratio at each time point in group Cis 1 ( P>0.05), and TOF ratio was significantly decreased at T 2-4 in group Cis 2 and at T 2-4 in group Cis 3 ( P<0.05). Compared with group Cis 1, TOF ratio was significantly decreased at T 3, 4 in group Cis 2 and at T 2-4 in group Cis 3 ( P<0.05). The effective elicitation rate of MEPs was 100% in the four groups.There was no significant difference in the incidence of intraoperative cardiovascular events, recovery of spontaneous breathing and body movement among the four groups ( P>0.05). Conclusion:Continuous intravenous infusion of cis-atracurium 0.833-1.000 μg·kg -1·min -1 can maintain a certain degree of muscle relaxation without affecting MEP monitoring in the patients undergoing intracranial aneurysm clipping.