Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова" (RU)
发明人:
Середенин Сергей Борисович (RU),Деева Ольга Алексеевна (RU),Гудашева Татьяна Александровна (RU),Яркова Милада Альнордовна (RU),Поварнина Полина Юрьевна (RU),Дурнев Андрей Дмитриевич (RU)
申请号：
RU2018143150
公开号：
RU2018143150A
申请日:
2018.12.06
申请国别(地区):
RU
年份:
2020
代理人:
摘要：
The invention relates to the field of biologically active compounds and concerns novel dipeptides of the formula R1-C(O)-X-AA1-Y-AA2-R2, where X=L or D configuration, Y=L or D configuration； АA1 is Trp or Gly； АA2 is Leu or Gly； and R1=C6H5-CH2- or С6Н5-(СН2)2- or СН3-(СН2)4-； R2=OH or ОСН3 or NH2 or NHCH3, possessing a spectrum of neurotropic activity, in particular anxiolytic and antidepressant activity. Anxiolytic activity of the claimed compounds was detected at doses of 0.1-1.0 mg/kg, and for the compound C6H5-(CH2)2C(O)-L-Trp-L-Leu-NH2 at doses of 0.01-5.00 mg/kg when administered intraperitoneally to BALB/c mice in an open field test with strobe light under emotional stress conditions. Additionally, anxiolytic activity for the compound C6H5-(CH2)2C(O)-L-Trp-L-Leu-NH2 at doses of 0.1-1.0 mg/kg was found in the elevated plus maze test in ICR mice. Using the selective antagonist PK11195, it was shown that the anxiolytic effect of the compound C6H5-(CH2)2C(O)-L-Trp-L-Leu-NH2 depends on binding with the 18-kDa protein TSPO. Antidepressant activity for the compound С6Н5-(СН2)2С(O)-L-Trp-L-Leu-NH2 was identified at doses of 0.01-0.05 mg/kg when administered intraperitoneally to BALB/c mice in the Porsolt forced swim test.
