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
α4β2nicotinic 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
^Peters L, Wright AD, Kehraus S, Gündisch D, Tilotta MC, König GM (October 2004). "Prenylated indole alkaloids from Flustra foliacea with subtype specific binding on NAChRs". Planta Medica. 70 (10): 883–886.
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^Sala F, Mulet J, Reddy KP, Bernal JA, Wikman P, Valor LM, et al. (January 2005). "Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite". Neuroscience Letters. 373 (2): 144–149.
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^Dukat M, Jain A, German N, Ferrara-Pontoriero R, Huang Y, Ma Y, et al. (December 2018). "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.
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Dukat M, Jain A, German N, Ferrara-Pontoriero R, Huang Y, Ma Y, et al. (December 2018). "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.
doi:
10.1021/acschemneuro.8b00156.
PMID30028943.
S2CID51704428.