Disease relevance of Epibatidine

• Even though the alpha4beta2 binding affinity of several of the analogues were equal to that of epibatidine, all of the compounds were weak agonists in the antinociceptive, hypothermia, and spontaneous activity test in mice [1].
• Likewise, spinal administration of epibatidine after the development of hyperalgesia not only significantly attenuated the decrease in PWL, but prevented further increases in knee joint swelling and temperature [2].
• The effects of epibatidine and nicotine were further investigated in human neuroblastoma SH-SY5Y cells (expressing alpha3, alpha5, beta2, and beta4 nAChR subunits) [3].
• Thus, the purpose of the present studies was to evaluate whether the neuronal nicotinic receptor agonist epibatidine possesses antihyperalgesic activity in the formalin model of facial pain [4].
• The toxicity of epibatidine, because of its nonspecificity for both peripheral and central nicotinic receptors, precludes its development as an analgesic [5].

Psychiatry related information on Epibatidine

• In contrast to morphine, epibatidine failed to increase locomotor activity [6].
• The response profile of epibatidine resembled that previously obtained with nicotine in that response accuracy was enhanced and omission errors and correct response latency decreased [7].
• The effect of (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT-418) and (2,4)-dimethoxybenzylidene anabaseine (GTS-21), two potential compounds for the treatment of Alzheimer's Disease, and of the natural product (+/-)epibatidine were compared to (-)nicotine [8].
• Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of Abeta1-42, but not related to plaque or tangle densities [9].

High impact information on Epibatidine

• Analysis of Aplysia AChBP complexes with nicotinic ligands shows that loop C, which does not significantly change conformation upon binding of the antagonist, methyllycaconitine, further opens to accommodate the peptidic antagonist, alpha-conotoxin ImI, but wraps around the agonists lobeline and epibatidine [10].
• Type 3 nAChRs bind epibatidine with high affinity in equilibrium binding experiments and show that cytisine is as effective as nicotine in electrophysiological experiments; their distribution and persistence in beta2 -/- mice strongly suggest a subunit composition of alpha3 beta4 [11].
• Type 4 nAChRs bind cytisine and epibatidine with high affinity in equilibrium binding experiments and persist in beta2 -/- mice; cytisine = nicotine in electrophysiological experiments [11].
• The nicotinic receptor binding the agonist epibatidine (the high affinity receptor subtype, consisting primarily of alpha3 and alpha4, together with beta2 receptor subunits) was significantly reduced by 40-50% in the granule cell, Purkinje and molecular layers in the autistic compared with the normal group (P < 0.05) [12].
• The effects of nicotine were equal to bFGF and were mimicked by epibatidine and blocked by hexamethonium [13].

Chemical compound and disease context of Epibatidine

• Our study describes the effects of SIB-1765F on locomotor activity in rats, which were compared to those observed for nicotine and epibatidine [14].
• Hydrochloride derivatives 5a-c and quaternary ammonium derivatives 6a-c of epibatidine incorporated with amino acid ester were synthesized and evaluated for their in vivo analgesic activity and toxicity [15].
• The favorable selective toxicity of neonicotinoid insecticides (represented here by imidacloprid, thiacloprid, and a nitromethylene analogue) for insects versus mammals is not shared by three of their N-unsubstituted imine derivatives or by nicotine or epibatidine [16].

Biological context of Epibatidine

• The present study examines binding of acetylcholine (ACh) and epibatidine, agonists with opposite selectivity for the two binding sites of mouse muscle AChRs [17].
• Point mutations reveal that three sequence differences within the gamma104-117/delta106-delta119 region are determinants of epibatidine selectivity: gammaLys104/deltaTyr106, gammaSer111/deltaTyr113, and gammaTyr117/deltaTyr119 [18].
• The epibatidine-induced up-regulation of nAChR binding sites in SH-SY5Y cells was one-fourth that in M10 cells [3].
• Complexes formed by alpha and mutant gamma(K34S+F172I) subunits bind epibatidine with increased affinity compared to alphagamma complexes, whereas the kinetics of alpha2betadeltagamma(K34S+F172I) receptors reveal no change in affinity of the low-affinity site, but increased affinity of the high-affinity site [19].
• Conformationally constrained epibatidine analogues 20a,b and 23a,b were synthesized using a radical cyclization as the key step [20].

Anatomical context of Epibatidine

• Using the high-affinity agonist epibatidine, we found similar differences in receptor number between strains in both in vitro ligand binding experiments with spinal cord membranes and in situ autoradiographic analyses [21].
• In rat adrenal glands, 5-iodo-A-85380 binds to nAChRs containing alpha3 and beta4 subunits with 1/1000th the affinity of epibatidine, and exhibits 1/60th and 1/190th the affinity of epibatidine at alpha7 and muscle-type nAChRs, respectively [22].
• Nicotine exhibited a 14 times lower affinity for the nAChRs in SH-SY5Y cells as compared with M10 cells, whereas epibatidine showed similar affinities for the nAChRs expressed in the two cell lines [3].
• The every tested dose of epibatidine administered into the locus coeruleus also produced freezing behavior immediately after injection, which was relatively short-lived compared to the analgesic effect [23].
• The present study tested the hypothesis that the serotonergic dorsal raphe nucleus is a site of action of epibatidine [24].

Associations of Epibatidine with other chemical compounds

• Methadone pretreatment induced up-regulation of epibatidine binding sites in SH-SY5Y cells [25].
• The structures of the novel epibatidine analogues were assigned on the basis of spectral data, that of compound 24 being additionally verified by X-ray crystallography exhibiting two racemic solid-state conformations in the crystal lattice and representing the first X-ray structure of an unprotected 7-azabicyclo[2.2.1]heptane moiety [26].
• Behavioral responses of rats to hindpaw formalin injection were compared after direct administration of epibatidine into the locus coeruleus (LC), and after subcutaneous administration [23].
• Nicotinic agonists, such as epibatidine (EPI) and A-85380, when administered systemically, elicit analgesia [27].
• Infusion of epibatidine into LC induced analgesia, which was reversed by prior infusion of mecamylamine into LC [23].

Gene context of Epibatidine

• Using Western blot analysis it was found that the epibatidine-induced upregulation of FGF-mRNA is accompaned by an increase of FGF-2 protein level at the 20-h time-interval [28].
• The binding of Epibatidine and alphaBungarotoxin, ligands for alpha3- and alpha7-containing receptors, respectively, revealed, for each ligand, a single class of high-affinity binding sites, with similar affinity in both wild-type and mdx mice [29].
• Development of muscarinic analgesics derived from epibatidine: role of the M4 receptor subtype [5].
• In human temporal cortex loss of acetylcholinesterase catalytic activity is positively correlated with decreased epibatidine binding and in a transgenic mouse model over expressing acetylcholinesterase, epibatidine binding is elevated [9].
• There were no significant differences between the groups for epibatidine binding or ChAT [30].

Analytical, diagnostic and therapeutic context of Epibatidine

• These epibatidine analogs have been shown previously to possess high binding affinity to alpha4beta2 but not to alpha7 nAChRs and to inhibit nicotine-induced analgesia in behavioral pain tests [31].
• Ligand binding and immunoprecipitation studies with subunit-specific antibodies showed that the expression of alphaBungarotoxin (alphaBgtx) and high-affinity epibatidine (Epi) receptors is regulated developmentally and increases until postnatal day 21 (P21) [32].
• Intrathecal injection of epibatidine alone did not alter pain behaviors, compared to vehicle-treated rats [33].
• The physiological effects of EP on pain-related behaviors and inflammation were tested after administration to the dorsal horn via a microdialysis fiber [2].
• The frog toxin epibatidine is one of the most powerful ligands of the neuronal nicotinic receptors and derivatives show promising possibilities for labeling in positron emission tomography studies [34].

References