Therapy Analysis - Drug addiction
Smoking and alcohol
...Even tobacco companies no longer dispute the addictive nature of nicotine, found in all tobacco productsEven tobacco companies no longer dispute the addictive nature of nicotine, found in all tobacco products. It leads to rapid activation of the dopamine reward system, particularly because smoking provides the perfect drug delivery vehicle. The field of smoking cessation therapies is already crowded, with multiple OTC products such as nicotine gums and patches available for the individual trying to quit. These therapies simply replace the nicotine a smoker would have received from cigarettes. For those who fail to kick the habit using this approach, the standard non-nicotine drug therapy until recently had been a sustained-release formulation of the antidepressant buproprion, marketed as Zyban by GlaxoSmithKline. Whilst the exact mechanism by which it produces anti-smoking effects is unknown, it is a weak inhibitor of both dopamine and noradrenaline reuptake. Recently, a second drug has become available, with Pfizer's launch of Champix/Chantix (varenicline tartrate), a partial agonist at the α4β2 nicotine receptor. Useful as these compounds are, they still only produce quit rates of less than 50%, and so drug development in this area continues apace. In late-stage trials currently are GlaxoSmithKline's GW-468816, an NMDA glycine site antagonist, and dianicline (SSR-591813), a nicotinic α4β2 partial agonist under development by Sanofi- Aventis. Using a very different approach, Celtic Pharma is developing an immunotherapy, TA-NIC. This vaccine induces production of antibodies against nicotine, thus preventing the nicotine from crossing the blood-brain barrier and hence removing the positively reinforcing effect. Acting in a similar fashion is Cytos Biotechnology's CYT002-NicQb, a nicotine vaccine in Phase II and recently partnered with Novartis.
In cases of chronic alcohol abuse, the standard drug therapy is the opioid receptor antagonist naltrexone (which is also used to treat opiate addiction, see later). It has been shown to reduce the frequency and severity of relapse to drinking, mediated, it is presumed, through modulation of the dopaminergic system usually activated by ethanol. A sustained-release formulation of naltrexone developed by Alkermes is also just becoming available in various markets, and BioTie's nalmefene tablet formulation is also waiting in the wings. A second drug currently prescribed for alcohol addiction is acamprosate. This acts in a very different way - it increases GABA-ergic transmission in the brain through the inhibition of EAA receptors. Much further back in the pipeline, CV Therapeutics is developing an aldehyde dehydrogenase 2 antagonist for the treatment of alcohol dependence, which is hoped to be an improvement on standard aversion therapy drugs such as disulfiram.
