Cytisine derivatives as ligands for neuronal nicotine receptors and with various pharmacological activities

Boido, Caterina Canu; Tasso, Bruno; Boido, Vito; Sparatore, Fabio

doi:10.1016/s0014-827x(03)00017-x

Cited by 97 publications

(53 citation statements)

References 41 publications

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“…4 Pharmacokinetic data derive mainly from animal studies. 15 16 Applied orally in rabbits, cytisine is well absorbed in the gut. The elimination half-life after oral administration is 52 minutes.…”

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confidence: 99%

An uncontrolled trial of cytisine (Tabex) for smoking cessation: Table 1

et al. 2006

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Objectives:Cytisine (Tabex) has been licensed in Eastern Europe as an aid to smoking cessation for 40 years. Cytisine is a partial agonist with high affinity binding to the α4β2 nicotinic acetylcholine receptor believed to be central to the rewarding effect of nicotine. There is insufficient information on effectiveness to warrant licensing by modern standards. To assess whether full-scale controlled trials are warranted, this study sought to obtain an estimate of the 12-month continuous abstinence rates of smokers using cytisine with minimal behavioural support.Design:An uncontrolled, open-label trial.Setting:A smokers’ clinic in an oncology centre in Warsaw, Poland.Subjects:436 consecutive attendees of the smokers’ clinic of whom 191 were male. The mean dependence score (Fagerstrom Test for Nicotine Dependence) was 6.1.Intervention:The standard regimen of Tabex (cytisine) was used, involving 25 days of treatment with minimal behavioural support.Main outcome measure:Self-reported continuous abstinence for 12 months; with abstinence verified by carbon monoxide at the final follow up (after 12 months).Results:60 participants (13.8% of the total sample) were abstinent for 12 months. Of the 315 subjects, who had taken the drug, 49 (15.5%) stopped cytisine because of adverse effects (mostly gastric disturbances and nausea), although they were not serious. The frequency of the minor adverse effects, primarily gastric disturbance, was similar to that observed in previous studies with the drug.Conclusions:The long-term abstinence rates were similar to those observed in smokers receiving nicotine replacement therapy. Full-scale randomised trials of cytisine (Tabex), conducted to the standards required by regulatory authorities, are warranted.

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An uncontrolled trial of cytisine (Tabex) for smoking cessation: Table 1

et al. 2006

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“…Nicotinic receptors form a family of acetylcholine (Ach)-gated cation channels made up of different subtypes, localized in the central and peripheral nervous systems [5,6]. Nicotine, a naturally occurring alkaloid, affects the functioning of peripheral nervous system.…”

Section: Introductionmentioning

confidence: 99%

“…Cytisine shows an affinity towards the specific subunits of nicotine acetylcholine receptors, nAChRs. It acts as a partial agonist at the α4β2 subunit, and very potently binds to the α3β4, α7 nicotinic subunits [5]. So, cytisine possesses a structure and mechanism of action that are similar to those of nicotine, but it has much lower toxicity [9,10].…”

Section: Introductionmentioning

confidence: 99%

Experimental studies of charge density distribution in the crystals of cytisine and N-methylcytisine. Inside the Fake Tobacco

2017

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The high-resolution X-ray data for two bioactive molecules: cytisine (1) and its N-methyl derivative (2) have been collected up to sinθ/λ = 1.12 Å −1 for 1 and 1.0 Å −1 for 2. This data was used for modeling of the fine features of electron density distribution, including bonding density and electron lone pairs. The quality of the model was checked by, e.g., rigid bond test and RDA analysis. The topological analysis (gradient field analysis) has been also performed for both inter-and intramolecular interactions. In case of 1 a number of intermolecular interactions, from relatively strong N-H···O hydrogen bonds to weak H···H contacts was found, and their topological features were analyzed. For N-methyl derivative, only few intermolecular bonding contacts were found. The analyzed features show that besides the structural similarities of both alkaloids, the electron density distribution and consequently all its derivatives differ quite significantly in places.

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“…In terms of analogues, manipulation of cytisine itself is readily achievable at C3 and C5, C10, and N12 [11][12][13][14][15][16][17][18][19][20] but interest in cytisine as a target for total synthesis has also been significant as well as the synthesis of cytisine derivatives [21,22].…”

Section: Introductionmentioning

confidence: 99%

The Role of Halogen Bonding in Crystal Structures of 3-Halogeno Cytisine Derivatives

Przybył

Kubicki

2012

J Chem Crystallogr

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The crystal structures of three 3-halogeno derivatives of 13N-substituted cytisine have been determined by X-ray diffraction. The two 13-acetyl substituted compounds, 3-bromo (1) and 3-iodo (2) are isostructural, with the isostructurality index as high as 99%. They both crystallize in monoclinic P2 1 space group, with unit cell parameters of a = 8.4709(10) Å , b = 9.2266(12) Å , c = 8.6051(10) Å , b = 98.528 (11)8 (1) and a = 8.2322(6) Å , b = 9.1724(7) Å , c = 8.5494(6) Å , b = 98.181 (7)8 (2). In turn, 3-bromo-13-t-butyl-carbonate derivative (3) crystallizes in orthorhombic P2 1 2 1 2 1 space group with a = 6.8171(3) Å , b = 7.8994(4) Å , c = 31.4657(15) Å . Conformation of the cytisine skeleton is similar in all three molecules, with almost planar A ring, sofa conformation of B-ring and C ring being an almost ideal chair. However, the orientations of the double C=O bonds in 13N-substituents are completely different: in 1 and 2 it is cis with respect to C12 (C12-N13-C14-O15 torsion angle is 3.3(4)8 in 1 and 1.3(6)8 in 2) while in 3 it is trans (-175.4(3)8). In the structures of 1 and 2 the driving force of the crystal architecture are quite strong C-HÁÁÁX halogen bonds with CÁÁÁX distances far shorter than the sums of van der Waals radii (CÁÁÁBr in 1 is 2.9430(19) Å and CÁÁÁI in 2 2.974(3)). In contrast in 3-partially as the consequence of different orientation of the substituent-there are no halogen bondings but instead some weak C-HÁÁÁO contacts organize the molecules into two-dimensional patterns.

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Cytisine derivatives as ligands for neuronal nicotine receptors and with various pharmacological activities

Cited by 97 publications

References 41 publications

An uncontrolled trial of cytisine (Tabex) for smoking cessation: Table 1

An uncontrolled trial of cytisine (Tabex) for smoking cessation: Table 1

Experimental studies of charge density distribution in the crystals of cytisine and N-methylcytisine. Inside the Fake Tobacco

The Role of Halogen Bonding in Crystal Structures of 3-Halogeno Cytisine Derivatives

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