Synthesis, antiulcer and antidepressive activity of 4-(4-halophenyl)-2-phenyl-1,2,3,4-tetrahydroisoquinolines.
4-(4-halophenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolines 2a-c have been synthesized by two methods and their biochemical and pharmacological properties have been studied. Biochemical investigations showed that all the compounds are strong inhibitors of DA, NE and 5-HT reuptake, the strongest effect being observed with compound 2b (R = Br). 2a-c exhibited a strong antiulcer activity on an experimental model of stress-induced ulcers with minimal doses (0.1 to 3.0 mg/kg), the effect of 2b being 30 times higher as compared to the H2-antagonist Ranitidin. At higher doses (10 to 30 mg/kg) 2b and 2c inhibited the Reserpinptosis. The most active compound in the reuptake inhibition 2b, expressed a high antidepressive activity in some other tests, comparable to that of the antidepressant Nomifensin. 2b has been selected for further pharmacological testing under the code name AN12.
Mondeshka
D M
DM
Technological University of Sofia, Bulgaria.
Angelova
I G
IG
Tancheva
C N
CN
Ivanov
C B
CB
Daleva
L D
LD
Ivanova
N S
NS
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000897:Anti-Ulcer Agents; D000928:Antidepressive Agents; D007546:Isoquinolines; D014179:Neurotransmitter Uptake Inhibitors