Epibatidine dihydrochloride

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.

Drugs were delivered s.c. in the midscapular region of the back or i.v. via chronic indwelling catheter in a volume of 0.1-1 ml/kg. Drug doses are expressed as the weight, in mg/kg, of the forms listed below, except in the case of nicotine, which is expressed as the weight of the free base. (-)-Nicotine hydrogen tartrate salt (Sigma-Aldrich), epibatidine dihydrochloride (Sigma-Aldrich), varenicline dihydrochloride (Research Technology Branch of the National Institute on Drug Abuse, Rockville, MD), cocaine hydrochloride (Sigma-Aldrich), midazolam hydrochloride (Bedford Laboratories, Bedford, OH), morphine sulfate (Research Technology Branch of the National Institute on Drug Abuse), mecamylamine (Waterstone Technology, Carmel, IN), dihydro-β-erythroidine hydrobromide (Tocris Bioscience, Bristol, UK), and methyllycaconitine citrate (Research Technology Branch of the National Institute on Drug Abuse) were dissolved in physiological saline. For nicotine, the amount of sodium hydroxide (Sigma-Aldrich) needed to adjust the pH of the solution to 7 was determined and figured into the calculation of volume for a desired concentration.