A substituted pyridopyrroloquinoxaline, or more specifically a substituted octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline, also known as a substituted heterocycle fused γ-carboline, is a further-cyclized and substituted tetracyclic derivative of the tricyclic alkaloid γ-carboline as well as an analogue of the atypical antipsychotic lumateperone. They can additionally be thought of as analogues of cyclized tryptamines like the β-carbolines or harmala alkaloids such as harmaline, but are not technically tryptamines themselves.
Pyridopyrroloquinoxalines are notable for their varying interactions with the serotonin 5-HT2A receptor as well as with other monoamine receptors. Lumateperone and deulumateperone are serotonin 5-HT2A receptor antagonists with antipsychotic properties, IHCH-7113 is a putatively psychedelic serotonin 5-HT2A receptor full agonist with a robust head-twitch response in rodents, and IHCH-7086, IHCH-7079, and ITI-1549 are putatively non-hallucinogenic β-arrestin-biased serotonin 5-HT2A receptor partial agonists with psychoplastogenic and/or antidepressant-like effects in preclinical studies. The broad receptor interactions of some of these compounds have been studied.
Pyridopyrroloquinoxalines with serotonin 5-HT2A receptor agonistic activity such as IHCH-7113 and IHCH-7086 were first described in the scientific literature by Dongmei Cao and colleagues by 2022. As of 2025, ITI-1549 is under development by Intra-Cellular Therapies for the treatment of mood and other psychiatric disorders.
List of pyridopyrroloquinoxalines
Structure Name Chemical name IHCH-7113 (6bR,10aS)-3-methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline IHCH-7079 (6bR,10aS)-2,3,6b,7,8,9,10,10a-octahydro-8-[2-(2-methoxyphenyl)ethyl]-3-methyl-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline IHCH-7086 (6bR,10aS)-2,3,6b,7,8,9,10,10a-octahydro-8-[3-(2-methoxyphenyl)propyl]-3-methyl-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline Lumateperone (ITI-007) 1-(4-fluorophenyl)-4-(3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-butanone Deulumateperone (ITI-1284) 1-(4-fluorophenyl)-4-[(6bR,10aS)-3-methyl-2,3,6b,9,10,10a-(2-2H)hexahydro(2-2H)-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl]butan-1-one ITI-1549 (6b'R,10a'S)-8'-[2-(1,2-benzoxazol-3-yl)ethyl]-2',3',6b',9',10',10a'-hexahydro-3'-methylspiro[cyclopropane-1,2'-[1H,7H]pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline]
Other known pyridopyrroloquinoxalines include IHCH-7081, IHCH-7087, IHCH-7088, IHCH-7089, IHCH-7112, and IHCH-7120.
Related compounds
Structure Name Chemical name 2MePI 2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Tiflucarbine 9-ethyl-4-fluoro-1-methyl-7,8,9,10-tetrahydro-6H-pyrido[4,3-b]thieno[3,2-e]indole IHCH-8134 (6bR,10aS)-8-(3-(2-methoxyphenyl)propyl)-1,2,6b,7,8,9,10,10a-octahydro-[1,4]oxazino[2,3,4-hi]pyrido[4,3-b]indole
See also Cyclized tryptamine Substituted β-carboline Ibogalog Substituted lysergamide Non-hallucinogenic 5-HT2A receptor agonist
References