JNJ-18038683 explained
| Iupac Name: | 1-benzyl-3-(4-chlorophenyl)-5,6,7,8-tetrahydro-4H-pyrazolo[3,4-d]azepine |
| Width: | 200 |
| Cas Number: | 851373-91-6 |
| Pubchem: | 11151899 |
| Chemspiderid: | 9327007 |
| Unii: | 28PGH5X4OQ |
| C: | 20 |
| H: | 20 |
| Cl: | 1 |
| N: | 3 |
| Smiles: | C1CNCCC2=C1C(=NN2CC3=CC=CC=C3)C4=CC=C(C=C4)Cl |
| Stdinchi: | 1S/C20H20ClN3/c21-17-8-6-16(7-9-17)20-18-10-12-22-13-11-19(18)24(23-20)14-15-4-2-1-3-5-15/h1-9,22H,10-14H2 |
| Stdinchikey: | UKJPMZGILXATGT-UHFFFAOYSA-N |
JNJ-18038683 is a potent and selective antagonist of the 5HT7 serotonin receptor discovered by Johnson & Johnson. It has nootropic and antidepressant effects in both animal and human studies and has progressed to Phase II trials as an adjunctive treatment for improving cognition and mood in stable bipolar disorder; it has been found to reduce REM sleep (the lightest stage of sleep, elevated in depression) in humans and block circadian rhythm phase-shift advances in mice.[1] [2]
It binds to the 5-HT6 serotonin receptor with 10x less affinity.[3] At relevant doses, inhibition of 5-HT6 would be expected to render pro-cognitive and anti-dementia effects.[4] [5]
Notes and References
- Bonaventure P, Dugovic C, Kramer M, De Boer P, Singh J, Wilson S, Bertelsen K, Di J, Shelton J, Aluisio L, Dvorak L, Fraser I, Lord B, Nepomuceno D, Ahnaou A, Drinkenburg W, Chai W, Dvorak C, Sands S, Carruthers N, Lovenberg TW . 6 . Translational evaluation of JNJ-18038683, a 5-hydroxytryptamine type 7 receptor antagonist, on rapid eye movement sleep and in major depressive disorder . The Journal of Pharmacology and Experimental Therapeutics . 342 . 2 . 429–440 . August 2012 . 22570363 . 10.1124/jpet.112.193995 . 10418102 .
- Shelton J, Yun S, Losee Olson S, Turek F, Bonaventure P, Dvorak C, Lovenberg T, Dugovic C . 6 . Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity . Frontiers in Behavioral Neuroscience . 8 . 453 . 2014 . 25642174 . 4295543 . 10.3389/fnbeh.2014.00453 . free .
- Web site: JNJ-18038683 FREE BASE. 2022-01-07. www.chemsrc.com. en.
- Andrews M, Tousi B, Sabbagh MN . 5HT6 Antagonists in the Treatment of Alzheimer's Dementia: Current Progress . Neurology and Therapy . 7 . 1 . 51–58 . June 2018 . 29728891 . 5990506 . 10.1007/s40120-018-0095-y . free .
- González-Vera JA, Medina RA, Martín-Fontecha M, Gonzalez A, de la Fuente T, Vázquez-Villa H, García-Cárceles J, Botta J, McCormick PJ, Benhamú B, Pardo L, López-Rodríguez ML . 6 . A new serotonin 5-HT6 receptor antagonist with procognitive activity - Importance of a halogen bond interaction to stabilize the binding . Scientific Reports . 7 . 1 . 41293 . January 2017 . 28117458 . 10.1038/srep41293 . 2017NatSR...741293G . free . 5259792 .
