(+)-Methamphetamine HCl, (±)-methylphenidate HCl, and (±)-mecamylamine HCl were provided by the National Institute on Drug Abuse Drug Supply Program (Bethesda, MD). Bruce Blough (RTI) synthesized (±)-bupropion HCl, 2S,3S-hydroxybupropion HCl and 2R,3R-hydroxybupropion HCl, using previously described methods (Lukas et al., 2010 (link)). (−)-Nicotine hydrogen bitartrate salt (Sigma Aldrich, St. Louis, MO) was dissolved in sterile water and sodium hydroxide was added to the solution to reach a pH of approximately 5-7. Risperidone (Sigma Aldrich) was dissolved in 2% lactic acid (85% w/w; Sigma Aldrich) and sodium hydroxide was added to reach a pH of approximately 5-6. All other drugs, including varenicline tartrate (Sigma Aldrich) were dissolved in sterile water. All drug doses are expressed as the salt forms listed above, except for nicotine and Risperidone, which were expressed as the base. Nicotine doses were expressed as the free base by multiplying the bitartrate dose by 0.325 (Matta et al., 2007 (link)).
Varenicline tartrate
Manufactured by Merck Group
Sourced in United States
Varenicline tartrate is a chemical compound used in the production of pharmaceutical products. It is a key ingredient in certain medication formulations. The core function of varenicline tartrate is to serve as an active pharmaceutical ingredient in the manufacturing process. No further details on intended use or application can be provided in an unbiased and factual manner.
Automatically generated - may contain errors
Lab products found in correlation
Risperidone, by Merck Group (1 mentions)
Nicotine hydrogen bitartrate salt, by Merck Group (1 mentions)
Lactic acid, by Merck Group (1 mentions)
Yohimbine hydrochloride, by Merck Group (1 mentions)
Nicotine bitartrate, by MP Biomedicals (1 mentions)
Bupropion hydrochloride, by LGC (1 mentions)
Serotonin hydrochloride, by Merck Group (1 mentions)
Mecamylamine hydrochloride, by Merck Group (1 mentions)
Acetylcholine chloride, by Merck Group (1 mentions)
Cytisine, by Merck Group (1 mentions)
Bupropion, by Merck Group (1 mentions)
Norepinephrine bitartrate, by Merck Group (1 mentions)
β nicotinamide adenine dinucleotide, by Merck Group (1 mentions)
Nicotinamide, by Merck Group (1 mentions)
Nornicotine, by Merck Group (1 mentions)
Cotinine, by Merck Group (1 mentions)
Hydrochloric acid (hcl), by Merck Group (1 mentions)
Ammonium formate, by Merck Group (1 mentions)
Methanol meoh, by Merck Group (1 mentions)
6 protocols using varenicline tartrate
1
Synthesis and Formulation of Psychoactive Drugs
2
Pharmacological Manipulation of Nicotine Responses
3
Competitive ELISA for Nicotine Selectivity
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The selectivity of the nic•mAbs 5G4, 7A8, 12F5, and 8D1 for S-(–)-nicotine was determined by competitive ELISA using 3’AM-S-(–)-Nic-pGlu-coated plates essentially as described above. Serial dilutions (in a blocking/diluent buffer of PBS + 1% non-fat dry milk) of competitors were added to the coated and blocked plates. Subsequently, the nic•mAb was added at a fixed concentration yielding a non-saturating A450 level in control wells without competitor. After 45 min incubation at 37°C, the plates were washed, and detection of bound nic•mAb was done as previously described. Small molecule competitors included S-(–)-nicotine, acetylcholine chloride, β-nicotinamide adenine dinucleotide (NAD), bupropion, S-(–)-cotinine, cytisine, dopamine (3-hydroxytyramine) hydrochloride, mecamylamine hydrochloride, nicotinamide, (±)-norepinephrine (+)-bitartrate, (±)-nornicotine, serotonin hydrochloride, and varenicline tartrate (all from Sigma). These compounds include neurotransmitters, nicotine metabolites, structurally similar compounds, and smoking cessation drugs. The cross-reactivity was calculated from the ratio of the IC50 values as follows: (IC50, nicotine/IC50, competitor) × 100%.
4
Quantification of Desmoxan and Nicotine Metabolites
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Desmoxan (capsules, CYT 1.5 mg) and standards of CYT were purchased from Aflofarm (Pabianice, Poland). Hydrochloric acid, ammonium 25%, formic acid (98–100%), ammonium formate, ACN, methanol (MeOH), and water for LC-MS were obtained from Merck (Darmstadt, Germany). Standards of cotinine and varenicline tartrate (internal standard, IS) were purchased from Sigma-Aldrich (Saint Louis, MO, USA).
5
Structural Insights into 5-HTBP Binding with Varenicline
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5-HTBP was expressed
and purified as previously described.10 (link) A stock solution of varenicline tartrate (Sigma) was made in water
at a concentration of 500 mM and mixed with 6 mg/mL 5-HTBP to yield
a final varenicline concentration of 5 mM. Cryoprotection of the crystals
was achieved by equilibration of the mother liquor in 5% increments
of glycerol to a final concentration of 30% glycerol, and crystals
were immersed in liquid nitrogen prior to X-ray diffraction data collection.
The structure was determined by molecular replacement using the published
structure of 5-HTBP as the template (PDB: 2YMD). After placing the ligand into the electron
density map, the model of the complex was manually rebuilt and refined
through iterative cycles in Coot and Phenix. The final model has an Rwork value of 18.7% and Rfree value of 24.4%. Model validation was carried out in Molprobity,
and the model has a score of 1.75, which is in the 97th percentile
for this resolution range. Figures were prepared with Pymol.
and purified as previously described.10 (link) A stock solution of varenicline tartrate (Sigma) was made in water
at a concentration of 500 mM and mixed with 6 mg/mL 5-HTBP to yield
a final varenicline concentration of 5 mM. Cryoprotection of the crystals
was achieved by equilibration of the mother liquor in 5% increments
of glycerol to a final concentration of 30% glycerol, and crystals
were immersed in liquid nitrogen prior to X-ray diffraction data collection.
The structure was determined by molecular replacement using the published
structure of 5-HTBP as the template (PDB: 2YMD). After placing the ligand into the electron
density map, the model of the complex was manually rebuilt and refined
through iterative cycles in Coot and Phenix. The final model has an Rwork value of 18.7% and Rfree value of 24.4%. Model validation was carried out in Molprobity,
and the model has a score of 1.75, which is in the 97th percentile
for this resolution range. Figures were prepared with Pymol.
6
Varenicline Sensitization and Conditioning
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