2,5-Dimethoxy-4-benzylamphetamine (DOBz or DOBN) is a serotonin 5-HT2 receptor modulator of the amphetamine and DOx families.[1][2][3] It is the DOx derivative with a benzyl ring at the 4 position.[1]

The drug's affinities (Ki) for the human serotonin 5-HT2 receptors have been found to be 0.40 nM for the serotonin 5-HT2A receptor, 24.5 to 35.0 nM for the serotonin 5-HT2B receptor, and 1.0 nM for the serotonin 5-HT2C receptor.[1][4] Its affinities for the serotonin 5-HT2 receptors are very similar to those of DOB.[1] The drug has been assessed and found to act as a silent antagonist of the serotonin 5-HT2B receptor (EmaxTooltip maximal efficacy = 0%).[4] In rodent drug discrimination tests, DOBz neither antagonized nor generalized to the stimulus of DOM.[5][6] Higher doses produced behavioral disruption however.[5]

DOBz was first described in the scientific literature by Richard Glennon and colleagues in 1989.[5][7]

See also

References

  1. ^ a b c d Nelson DL, Lucaites VL, Wainscott DB, Glennon RA (January 1999). "Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors". Naunyn Schmiedebergs Arch Pharmacol. 359 (1): 1–6. doi:10.1007/pl00005315. PMID 9933142.
  2. ^ Blaazer AR, Smid P, Kruse CG (September 2008). "Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors". ChemMedChem. 3 (9): 1299–1309. doi:10.1002/cmdc.200800133. PMID 18666267. Studies on the homologation of phenylisopropylamines at the 4-position found a decrease of in vivo hallucinogenic potency beyond n-propyl.[163] Yet later work using [3 H]ketanserin as a radioligand for 5-HT2 receptors in rat brain homogenate revealed significantly increased binding affinities with the more lipophilic derivatives; n-hexyl and n-octyl derivatives showed the highest binding affinity. After in vitro testing, these derivatives were found to act as 5-HT2 receptor antagonists.[67] Using [125I]DOI labeled human receptor data, the highest binding affinity at 5-HT2A receptors was found for the 4-nhexyl analogue DOHx (21, Ki=0.1 nm), followed by the 4- benzyl analogue DOBz (22, Ki=0.4 nm), DOB (16, Ki=0.6 nm), DOI (17, Ki=0.7 nm), and the 4-n-propyl analogue DOPR (23, Ki=0.9 nm).[63]
  3. ^ Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chem Rev. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID 38033123. Replacing the halogen on the 4-position with a methyl group led to significantly reduced activity (91, DOM, Ki = 100 nM), but the activity could be restored with longer linear alkyl chains and the benzyl group, such as compounds DOPR (92, Ki = 0.9 nM), DOHx (93, Ki = 0.1 nM), and DOBz (94, Ki = 0.4 nM).172 Interestingly, these DOXs compounds also exhibited some selectivity against the 5- HT2BR and 5-HT2CR.172
  4. ^ a b Hemanth P, Nistala P, Nguyen VT, Eltit JM, Glennon RA, Dukat M (2023). "Binding and functional structure-activity similarities of 4-substituted 2,5-dimethoxyphenyl isopropylamine analogues at 5-HT2A and 5-HT2B serotonin receptors". Front Pharmacol. 14: 1101290. doi:10.3389/fphar.2023.1101290. PMC 9902381. PMID 36762110.
  5. ^ a b c Glennon RA, Seggel MR (14 November 1989). "Interaction of Phenylisopropylamines with Central 5-HT2 Receptors: Analysis by Quantitative Structure—Activity Relationships". Probing Bioactive Mechanisms. Vol. 413. Washington, DC: American Chemical Society. pp. 264–280. doi:10.1021/bk-1989-0413.ch018. ISBN 978-0-8412-1702-7.
  6. ^ Glennon RA (1989). "Stimulus properties of hallucinogenic phenalkylamines and related designer drugs: formulation of structure-activity relationships" (PDF). NIDA Res Monogr. 94: 43–67. PMID 2575229.
  7. ^ Seggel MR, Yousif MY, Lyon RA, Titeler M, Roth BL, Suba EA, Glennon RA (March 1990). "A structure-affinity study of the binding of 4-substituted analogues of 1-(2,5-dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors" (PDF). J Med Chem. 33 (3): 1032–1036. doi:10.1021/jm00165a023. PMID 2308135.


Allikas: https://en.wikipedia.org/wiki/DOBz
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