1.Construction Exploration of a Team of Professional Drug Inspectors in Hubei Province
Yu SUN ; Yu ZHANG ; Xiaocui WEI ; Xuehui ZHANG ; Siyi LV ; Hui CHEN
China Pharmacist 2018;21(10):1835-1837
Objective: To explore the ways to build a team of professional drug inspectors in Hubei province in oder to improve the quality and effectiveness of drug inspections in our province, reduce the risk of supervision, and ensure the safety of people's drug use. Methods: The requirements of national regulations and policies for the inspectors were interpreted, the construction system of profes-sional drug inspectors in Shanghai drug review and verification center was selected as comparison, the current situation and existing problems of the construction of drug inspectors in our province were analyzed, and the construction methods of professional inspectors in Hubei province were found out. Results: On the basis of the existing team of drug inspectors, a standardized system for selection, training, evaluation and grading of drug inspectors should be established, and the establishment of a team of professional drug inspec-tors in our province should be gradually completed. Conclusion: Our province can gradually establish a team of professional drug in-spectors, firstly from the current "main part-time assisted by full-time" to " lay equal stress on part-time and full-time", and then to"main full-time assisted by part-time", till the final realization of all professional drug inspectors.
2.Carbazole and tetrahydro-carboline derivatives as dopamine D3 receptor antagonists with the multiple antipsychotic-like properties.
Zhongtang LI ; Fan FANG ; Yiyan LI ; Xuehui LV ; Ruqiu ZHENG ; Peili JIAO ; Yuxi WANG ; Guiwang ZHU ; Zefang JIN ; Xiangqing XU ; Yinli QIU ; Guisen ZHANG ; Zhongjun LI ; Zhenming LIU ; Liangren ZHANG
Acta Pharmaceutica Sinica B 2023;13(11):4553-4577
Dopamine D3 receptor (D3R) is implicated in multiple psychotic symptoms. Increasing the D3R selectivity over dopamine D2 receptor (D2R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D3R selective ligands. Through a structure-based virtual screen, ZLG-25 (D3R Ki = 685 nmol/L; D2R Ki > 10,000 nmol/L) was identified as a novel D3R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D3R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD3R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.