Chemistry:Desformylflustrabromine
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| Formula | C16H21BrN2 |
| Molar mass | 321.262 g·mol−1 |
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Desformylflustrabromine (dFBr) is a monomethyltryptamine derivative which was first isolated as a secondary metabolite of the marine bryozoan Flustra foliacea.[1]
Bioactivity
dFBr has been identified as a novel positive allosteric modulator of neuronal nicotinic acetylcholine receptor with sub-type specificity for heteromeric receptor with no effect on homomeric sub-type.[2] A recent study has been published which describes the synthesis of water-soluble salts of dFBr and its action has been confirmed as selective potentiator of α4β2 nicotinic acetylcholine receptor responses by using two-electrode voltage clamp whole cell recordings.[3] In the year 2002 it was reported that dFBr was cytotoxic on human colon cancer cell line HCT 116.[4]
Desformylflustrabromine has also been found to be a positive allosteric modulator for the α2β2 subtype of neuronal nicotinic acetylcholine receptor. Additionally it relieves the inhibition of both α2β2 and α4β2 nicotinic acetylcholine receptors by β-Amyloid (1–42) Peptide.[5] Thus desformylflustrabromine can potentially be used in the treatment of Alzheimer's disease. Many of the analogues and derivatives of dFBr are reported to have a potentiating effect on the α4β2 receptors.[6][7]
Modulation of nicotinic acetylcholine receptor function by desformylflustrabromine has also been found to produce analgesic and anti-allodynic effects in animal models, which could potentially make it of interest for the treatment of neuropathic pain.[8][9] Anti-addictive and pro-cognitive actions have also been demonstrated.[10][11] Furthermore, limited experimental data suggests a potential use in treating the compulsive behaviors seen in OCD.[12]
References
- ↑ "Prenylated indole alkaloids from Flustra foliacea with subtype specific binding on NAChRs". Planta Medica 70 (10): 883–886. October 2004. doi:10.1055/s-2004-832610. PMID 15490312.
- ↑ "Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite". Neuroscience Letters 373 (2): 144–149. January 2005. doi:10.1016/j.neulet.2004.10.002. PMID 15567570.
- ↑ "Synthesis of desformylflustrabromine and its evaluation as an alpha4beta2 and alpha7 nACh receptor modulator". Bioorganic & Medicinal Chemistry Letters 17 (17): 4855–4860. September 2007. doi:10.1016/j.bmcl.2007.06.047. PMID 17604168.
- ↑ "Isolation and structure elucidation of deformylflustrabromine from the North Sea bryozoan Flustra foliacea". Zeitschrift für Naturforschung C 57 (11–12): 1056–1061. 2002. doi:10.1515/znc-2002-11-1218. PMID 12562094.
- ↑ "Allosteric modulator Desformylflustrabromine relieves the inhibition of α2β2 and α4β2 nicotinic acetylcholine receptors by β-amyloid(1-42) peptide". Journal of Molecular Neuroscience 45 (1): 42–47. September 2011. doi:10.1007/s12031-011-9509-3. PMID 21424792.
- ↑ "Deconstruction of the α4β2 nicotinic acetylcholine receptor positive allosteric modulator desformylflustrabromine". Journal of Medicinal Chemistry 54 (20): 7259–7267. October 2011. doi:10.1021/jm200834x. PMID 21905680.
- ↑ "des-Formylflustrabromine (dFBr): A Structure-Activity Study on Its Ability To Potentiate the Action of Acetylcholine at α4β2 Nicotinic Acetylcholine Receptors". ACS Chemical Neuroscience 9 (12): 2984–2996. December 2018. doi:10.1021/acschemneuro.8b00156. PMID 30028943.
- ↑ "Allosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain". European Journal of Pain 22 (1): 84–93. January 2018. doi:10.1002/ejp.1092. PMID 28809075.
- ↑ "Acute Administration of Desformylflustrabromine Relieves Chemically Induced Pain in CD-1 Mice". Molecules 24 (5): 944. March 2019. doi:10.3390/molecules24050944. PMID 30866543.
- ↑ "Reversal of Nicotine Withdrawal Signs Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Male Mice". Nicotine & Tobacco Research 20 (7): 903–907. June 2018. doi:10.1093/ntr/ntx183. PMID 29059422.
- ↑ "Desformylflustrabromine, a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors, enhances cognition in rats". Pharmacological Reports 72 (3): 589–599. June 2020. doi:10.1007/s43440-020-00092-4. PMID 32207091.
- ↑ "Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice". Frontiers in Behavioral Neuroscience 10: 244. 2016. doi:10.3389/fnbeh.2016.00244. PMID 28105008.
Further reading
- "des-Formylflustrabromine (dFBr): A Structure-Activity Study on Its Ability To Potentiate the Action of Acetylcholine at α4β2 Nicotinic Acetylcholine Receptors". ACS Chemical Neuroscience 9 (12): 2984–2996. December 2018. doi:10.1021/acschemneuro.8b00156. PMID 30028943.
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