Subjects in the TA-NIC vaccine trial were immunized with 4 doses over the first 8 weeks and then given a booster dose at 32 weeks. All subjects were encouraged to quit smoking after 12 weeks of the trial, and at 12 months, the quit rate in the highest-dose group significantly exceeded the control group (38% vs 8%).50 Based on these studies suggesting that high antibody titers correlate with smoking cessation, evaluation of nicotine conjugate vaccines are progressing Inhibitors,research,lifescience,medical and a phase Ilb/III trial was recently announced for NicQb.51 Alcohol Alcohol dependence is a major cause of morbidity and mortality in the United States and throughout the world. Acute PR-171 clinical trial withdrawal Inhibitors,research,lifescience,medical from alcohol

is a serious medical condition which can precipitate adrenergic activation, seizures, or delirium tremens, the last condition leading to 15% mortality when untreated.52 Many medications have been evaluated for the treatment of alcohol dependence

in recent years, including those that interact with dopaminergic, serotonergic, opioid, glutamate, and γ-aminobutyric acid (GABA) systems. Acute withdrawal Benzodiazepine Inhibitors,research,lifescience,medical use is the standard approach to treating withdrawal symptoms such as irritability, autonomic hyperactivity, and seizures associated with alcohol detoxification. Benzodiazepines act at GABA-A receptors to stimulate GABA release and gradually detoxify the patient from alcohol, thus avoiding associated withdrawal symptoms.53 The current

standard approach to alcohol detoxification uses tapering dosages of benzodiazepines such as chlodiazepoxide, clonazepam, diazepam, oxazepam, or lorazepam.54,55 Anticonvulsants, including carbamazepine and valproate, have also been studied Inhibitors,research,lifescience,medical for their efficacy in alcohol withdrawal treatment.6 Carbamazepine has been widely used in alcohol withdrawal. Inhibitors,research,lifescience,medical Carbamazepine has demonstrated its superiority to placebo in the speed of onset to relieve alcohol withdrawal symptoms such as tremor, sweating, palpitations, sleep disturbances, depression, anxiety, and anorexia.56 Furthermore, studies have also demonstrated that higher success rates and reduction in withdrawal symptoms in patients treated with carbamazepine than with benzodiazepines.57-59 Org 27569 Relapse prevention ami maintenance Disulfiram, acamprosate, oral naltrexone, and extended-release injectable naltrexone have FDA approval for the treatment of alcohol dependence. Disulfiram is the first agent to be approved for treatment of alcohol dependence and has been used for over 40 years. It acts as an alcohol-sensitizing agent, creating an aversion to alcohol. Disulfiram is an irreversible inhibitor of the enzymatic conversion of acetalaldehyde to acetic acid. Accumulation of acetalaldehyde results in the disulfiram-alcohol reaction: hypotension, flushing, nausea, and vomiting.