A novel compound called 4-F-PCP, structurally similar to ketamine and an NMDA receptor antagonist, shows antidepressant-like effects in mice. Doses of 3 and 10 mg/kg produced rapid and sustained effects, and repeated treatments remained effective. The compound reversed depression-related changes in synaptic plasticity proteins and altered excitatory amino acid transporters. At a 3 mg/kg dose, 4-F-PCP did not impair cognitive function in mice after up to 21 days of treatment. These findings suggest that 4-F-PCP may offer a faster-acting antidepressant with fewer side effects, though further research is needed.
The serotonin 2A receptor (5-HT2AR) is involved in drug addiction and psychiatric disorders. This study examined how the chemical structures of phenethylamine and tryptamine derivatives affect their binding to 5-HT2AR. Phenethylamines showed higher binding affinity than tryptamines. For phenethylamines, adding alkyl or halogen groups at the para position of the phenyl ring improved binding, while oxygen-containing groups had mixed effects depending on their position. For tryptamines, oxygen-containing groups on the larger ring increased affinity, but alkyl groups on the smaller ring and ally groups on the nitrogen decreased it. Functional tests indicated that compounds with higher affinity also showed stronger activation of signaling pathways and receptor internalization, suggesting they act as agonists. These findings guide the design of new 5-HT2AR ligands for treating psychiatric disorders and drug abuse.