Cytisine

Manufactured by Merck Group

Sourced in United States

Cytisine is a laboratory compound used in research applications. It is a naturally occurring alkaloid with a chemical structure similar to nicotine. Cytisine has been studied for its potential pharmacological properties, but its core function is as a research tool for scientific investigation. A detailed, unbiased, and factual description of Cytisine's intended use or applications is not available.

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Lab products found in correlation

20 protocols using cytisine

Radioactive Nicotinic Acetylcholine Receptor Assay

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[¹²⁵I]-Epibatidine was obtained from Perkin-Elmer NEN, Boston, MA. NaCl, KCl, MgSO₄, CaCl₂, Na₂HPO₄, NaH₂PO₄, bovine serum albumin, polyethyleneglycol, polyethylenimine, nicotine, and cytisine were obtained from Sigma Chemical Co., St. Louis, MO. 5I-A-85380 was purchased from Tocris Bioscience, Bristol, UK. Ketamine, xylazine, acepromazine and buprenorphine were obtained from MWI Veterinary Supply, Nampa, ID. Sucrose was obtained from Roche Diagnostics, Indianapolis, IN. HEPES and NaHEPES (products of BDH) and silastic tubing (a product of Dow Chemical) were obtained through VWR International, Denver, CO. Glass filters Type B were products of MicroFiltration Systems, Dublin, CA and glass fiber filters Type A/E were products of Pall Life Sciences, Port Washington, NY. Nylon mesh and 22 gauge stainless steel tubing were obtained from AmazonSupply.com.

Meyers E.E., Loetz E.C, & Marks M.J. (2015). Differential expression of the beta4 neuronal nicotinic receptor subunit affects tolerance development and nicotinic binding sites following chronic nicotine treatment. Pharmacology, biochemistry, and behavior, 130, 1-8.

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Characterizing Nicotinic Agonists Binding

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Experiments were performed on an Affinity ITC (TA instruments, New Castle, DE) at 25°C. The iDrugSnFR protein was buffer-exchanged into 3× PBS, pH 7.0. The nicotinic agonists were dissolved in the same buffer. 800 µM cytisine (Sigma-Aldrich, Munich, Germany) was titrated into 80 µM iCytSnFR, 160 µM 10-fluorocytisine was titrated into 16 µM iCyt_F_SnFR. 470 µM 9-bromo-10-ethylcytisine was titrated into 47 µM iCyt_BrEt_SnFR. 1.5 mM dianicline (Tocris, Bio-Techne, Minneapolis, MN) was titrated into 150 µM iDianiSnFR. Analysis, including correction for changes in enthalpy generated from the dilution of the ligands, was performed using a single-site binding model in the manufacturer’s NanoAnalyze software.

Nichols A.L., Blumenfeld Z., Fan C., Luebbert L., Blom A.E., Cohen B.N., Marvin J.S., Borden P.M., Kim C.H., Muthusamy A.K., Shivange A.V., Knox H.J., Campello H.R., Wang J.H., Dougherty D.A., Looger L.L., Gallagher T., Rees D.C, & Lester H.A. (2022). Fluorescence activation mechanism and imaging of drug permeation with new sensors for smoking-cessation ligands. eLife, 11, e74648.

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Hypoglycemic Effects of Drug Combinations

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To explore the hypoglycemic activity of drugs, experiment was conducted on normal and diabetic mice, which were maintained on the same HFD. Normal mice were injected with saline (group NS), while diabetic mice were randomly assigned to one of the five groups including saline (group SS), insulin (group SI), Trolox C (group ST), Cytisine (group SC) and combination of Trolox C and Cytisine (group STC). Each group contains 10–14 mice. Cytisine (1 mg/kg, i.p., Sigma Aldrich) and Trolox C (50 mg/kg, i.p., Sigma Aldrich) were freshly diluted in phosphate buffered saline (pH 7.1) from stock solutions. Saline and drugs were administrated intraperitoneally every day (between 9 and 11 a.m.) for the entire four-week period. Body weight and fasting blood from mouse tails were measured before (pretreatment) drug administration and 1–4 weeks after drug or saline administration, respectively. An intraperitoneal glucose tolerance test (IPGTT) was conducted by intraperitoneal injection of a 20% glucose solution with the dose of 2 g kg⁻¹ body weight. Both IPGTT and total area under the curve (AUC) were measured every two weeks. This study had been approved by the Animal Care Committee of the Peking University Health Science Center and all animal experiments were performed in compliance with the “Guidelines for Animal Experiment”.

Jin L., Tu J., Jia J., An W., Tan H., Cui Q, & Li Z. (2014). Drug-repurposing identified the combination of Trolox C and Cytisine for the treatment of type 2 diabetes. Journal of Translational Medicine, 12, 153.

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Radioligand Binding Assay for Nicotinic Receptors

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D-MEM and Penicillin/streptomycin were purchased from Quality Biologicals
(Gaithersburg, MD). Fetal Bovine serum was obtained from Atlanta Biologicals
(Lawrenceville, Ga). [³H]-Epibatidine (>97
%) was purchased from Perkin Elmer (Waltham, MA). IAM (immobilized
artificial membrane) particles were purchased from Regis Technologies Inc
(Morton Grove, IL). Hygromycin (80%) was obtained from Amresco (Solon,
OH). The HR 5/2 glass columns were purchased from Amersham Pharmacia Biotech
(Uppsala, Sweden). Tris-HCl and NaCl (>99 %) were obtained from
Fischer Scientific (Jessup, MD). MgCl₂ (≥ 98%),,
CaCl₂ (≥ 99%), KCl (>99 %), Sodium
cholate hydrate (>99 %),, Leupeptin (> 90%), Ammonium
acetate (>99 %), Benzamidine hydrochloride (>99 %),
Phenylmethanesulfonyl fluoride (PMSF, ≥98.5%), G418, Nicotine
(> 99%), Cytisine (≥ 99%), NorNicotine (≥
98%), Anabasine (≥ 97%), Mecamylamine hydrochloride
(> 96%), Bupropion hydrochloride (≥ 98%), and all
other chemicals were purchased from Sigma-Aldrich unless otherwise stated (St.
Louis, MO). Club Moss (Lycopodium clavatum L).
aqueous-alcoholic extract was from Hawaii Pharm (Honolulu, Hawaii) and
Trigonella foenum-graecum L. aqueous-alcoholic extracts
wasfrom Herb Pharm (Williams, OR).

Ciesla L., Okine M., Rosenberg A., Dossou K.S., Toll L., Wainer I.W, & Moaddel R. (2015). Development and characterization of the α3β4α5 nicotinic receptor cellular membrane affinity chromatography column and its application for on line screening of plant extracts. Journal of chromatography. A, 1431, 138-144.

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Nicotine Receptor Ligand Protocol

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Figure 1 shows the chemical structure of each drug, except nicotine, included in the study. (–)-Nicotine hydrogen tartrate salt, cytisine and epibatidine dihydrochloride were obtained from Sigma Chemical (St. Louis, MO). Varenicline dihydrochloride was obtained from the Research Technology Branch of the National Institute on Drug Abuse (Rockville, MD), mecamylamine from Waterstone Technology (Camel, IN) and dihydro-β-erythroidine hydrobromide from Tocris (Minneapolis, MN). 2′-Fluorodeschloroepibatidine (RTI-7527-36), 3′-(3″-dimethylaminophenyl) epibatidine (RTI-7527-76), and 2′-fluoro-(4-nitrophenyl) deschloroepibatidine (RTI-7527-102) were synthesized at the Center for Organic and Medicinal Chemistry, Research Triangle Institute (Research Triangle Park, NC) according to methods previously described (Carroll et al., 2004 (link), 2005 (link), 2010 (link)). Drugs were dissolved in 0.9% physiological saline and administered s.c. (except mecamylamine which was administered i.p.) in a volume of 10 ml/kg. Nicotine dose is expressed in terms of the weight of the free base; dose of other drugs is expressed as the weight of the base and salt.

Rodriguez J.S., Cunningham C.S., Moura F.B., Ondachi P., Carroll F.I, & McMahon L.R. (2014). Discriminative stimulus and hypothermic effects of some derivatives of the nAChR agonist epibatidine in mice. Psychopharmacology, 231(23), 4455-4466.

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Radioligand Binding Assay for nAChRs

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Dihydro-β-erythroidine hydrobromide (DHβE) and mecamylamine hydrochloride were purchased from Tocris (Bristol, UK). Sazetidine-A [6-(5-(((S)-azetidin-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] (Xiao et al., 2006 (link)), also known as AMOP-H-OH, was a generous gift from Dr. Alan P. Kozikowski (University of Illinois, Chicago, IL). [¹²⁵I]mAb 295 was provided by Dr. Jon M. Lindstrom (University of Pennsylvania, Philadelphia, PA). All other reagents and pharmacological ligands (acetylcholine chloride (ACh), (−)-nicotine hydrogen tartrate salt and cytisine) were purchased from Sigma (St. Louis, MO) unless otherwise specified. Fresh solution stocks were made daily and diluted as required.

Weltzin M.M., Lindstrom J.M., Lukas R.J, & Whiteaker P. (2015). Distinctive effects of nicotinic receptor intracellular-loop mutations associated with nocturnal frontal lobe epilepsy. Neuropharmacology, 102, 158-173.

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Pharmacological Modulation of Neuronal Receptors

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Drugs were diluted to final concentrations in bath solution from stock solutions at least 1000 times greater than the highest concentration employed. Capsaicin, cytisine, HC-030031(HC3), nicotine, mecamylamine, methyllycaconitine (MLA) were purchased from Sigma-Aldrich (St. Louis, MO). Stock solution of Capsaicin (10 mM) and mecamylamine (10 mM) were made in 100% ethanol, stock solution of cytisine (100 mM) and HC3 (100 mM) were made in DMSO. Stock solution of MLA (1mM) was made in water. Nicotine (30 mM or 100 mM) was diluted in bath solution just prior to use to concentrations between 1 μM and 1 mM. The α7 nAChR subunit selective antagonist MLA was used at a concentration of 20 nM ^{12 (link)}. The TRPA1 selective antagonist HC3 was used a final concentration of 10 μM based on results from our previous study ^{35 (link)}. The α3β4 nAChR subunit selective agonist cytisine was applied at a concentration of 100 μM ^{12 (link)}. The TRPV1 selective agonist Capsaicin was used at a final concentration of 500 nM.

Zhang X., Hartung J.E., Friedman R.L., Koerber H.R., Belfer I, & Gold M.S. (2019). Nicotine-evoked currents in human primary sensory neurons. The journal of pain : official journal of the American Pain Society, 20(7), 810-818.

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Nicotinic Receptor Ligands: Characterization

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(−)-Nicotine hydrogen tartrate and (−)-cytisine [CYT] were purchased from Sigma (St. Louis, MO, USA). Bupropion hydrochloride [BUP] was purchased from Toronto Research Chemicals (Toronto, ON, Canada). S-(−)-nornicotine fumarate [NOR] was provided by Girindus America, Inc. (Cincinnati, OH, USA). PHA-543613 [PHA], sazetidine-A [SAZ-A], and PNU-120596 [PNU] were gifts from the National Institute on Drug Abuse (Research Triangle Institute, Research Triangle Park, NC, USA). Nicotine doses are reported as free base equivalent, whereas all other compounds are reported in salt form. The vehicle, route of administration, injection volume, and injection-to-placement interval (IPI) for each compound are detailed in Table 1.

Charntikov S., Falco A.M., Fink K., Dwoskin L.P, & Bevins R.A. (2016). THE EFFECT OF SAZETIDINE-A AND OTHER NICOTINIC LIGANDS ON NICOTINE CONTROLLED GOAL-TRACKING IN FEMALE AND MALE RATS. Neuropharmacology, 113(Pt A), 354-366.

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Cytisine Neuroprotection in 6-OHDA Mouse Model

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Figure 1A shows the protocol for in vivo experiments in mice. Starting one week prior to 6-OHDA treatment (day −7), female and male mice were injected intraperitoneally (i.p), on alternate days, with 200 μl of either 0.9% normal saline or 0.2 mg/kg -(−) cytisine (Sigma), dissolved in 0.9% normal saline. Mice were weighed on alternate days, just prior to i.p. cytisine or saline injections and over the course of the entire experiment. Behavioral assays were performed on days −7 (baseline), 7, 14, and 21 where day 0 is the time point for 6-OHDA injection. After testing on day 21 all mice were deeply anesthetized with isoflurane and perfused with 10% formalin. Following perfusion, midbrain sections were collected for quantification of SNc DA neurons after tyrosine hydroxylase (TH) immunostaining.

Zarate S.M., Pandey G., Chilukuri S., Garcia J.A., Cude B., Storey S., Salem N.A., Bancroft E.A., Hook M, & Srinivasan R. (2021). Cytisine is neuroprotective in female but not male 6-hydroxydopamine lesioned parkinsonian mice and acts in combination with 17-β-estradiol to inhibit apoptotic endoplasmic reticulum stress in dopaminergic neurons. Journal of neurochemistry, 157(3), 710-726.

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Nicotine and Acetylcholine Receptor Ligand Assay

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(−)-Nicotine bitartrate, nicotine freebase, acetylcholine (ACh) iodide, diisopropyl fluorophosphate (DFP), NaCl, KCl, CaCl₂, MgSO₄, glucose, sucrose, HEPES, tetrodotoxin, polyethelenimine, bovine serum albumin (BSA), and cytisine were purchased from Sigma-Aldrich Chemical Co (St. Louis, MO). The radioisotopes [³H]-dopamine (7,8-³H at 20–40 Ci/mmol), carrier-free ⁸⁶RbCl (initial specific activity 13.6–18.5 Ci/μg), and [¹²⁵I]-epibatidine (2200 Ci/mmol) were purchased from Perkin Elmer (Waltham, MA). α-Conotoxin MII (α-CtxMII) was generously provided by J. Michael McIntosh, University of Utah, Salt Lake City, UT.

Buck J.M., Sanders K.N., Wageman C.R., Knopik V.S., Stitzel J.A, & O’Neill H.C. (2019). Developmental nicotine exposure precipitates multigenerational maternal transmission of nicotine preference and ADHD-like behavioral, rhythmometric, neuropharmacological, and epigenetic anomalies in adolescent mice. Neuropharmacology, 149, 66-82.

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