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 K_i = 685 nmol/L; D₂R K_i > 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.

Anoctamin 1 (ANO1) is a kind of calcium-activated chloride channel involved in nerve depolarization. ANO1 inhibitors display significant analgesic activity by the local peripheral and intrathecal administration. In this study, several thiophenecarboxylic acid and benzoic acid derivatives were identified as novel ANO1 inhibitors through the shape-based virtual screening, among which the 4-arylthiophene-3-carboxylic acid analogues with the best ANO1 inhibitory activity were designed, synthesized and compound

Objective To investigate the effects of psychological intervention on the obedience to medical orders and social support availability of hypertension patients in retired military cadres, then to further study its effects on their life quality.Methods Eighty-five retired military cadres, who were diagnosed as hypertension patients, were randomly divided into 2 groups:the study group and the control group.The patients in the control group were given routine drug treatment and general medical advice, while the patients in the study group received psychological intervention, in addition to the above treatment measures.They were surveyed by using Social Support Scale, Quality of Life Questionnaire (SF-36) and General Information Questionnaire both before and after intervention, and had one-year medical follow-ups.Results (1) With the exception of objective support, the scores of the study group were all significantly higher than those of the control group, with statistical significance (P<0.01).With the exception of objective support, the scores of the study group after intervention were significantly higher than those before intervention, also with statistical significance (P<0.01).(2) After inter-vention, the obedience to medical orders by the study group was superior to that of the control group, with statistical significance ( P<0.01).(3)After intervention, the scores of physiological function, health status, vigor, social function, emotional function and mental health in the study group were all higher than those in the control group , and statistical significance could be found, when comparisons were made between the 2 groups(P<0.05-0.01).Furthermore, the scores of the above indicators were higher than those before treat-ment, with statistical significance(P<0.05 ~0.01).(4) Obedience to medical orders behavior, social support availability, disease course and subjective support for the study group were put into the regression equation of the influential factors QOL, which could signifi-cantly predict the life quality of the patients.Conclusion Psychological intervention could obviously improve obedience to medical orders
and social support availability in hypertension patients among retired military cadres, thus effectively improving their life quality.