Antidepressants dopaminergic system

With regard to the specific action of antidepressants on the dopaminergic system, there is evidence that buproprion (not marketed in most countries in Western Europe as an antidepressant but available in North America), amineptine and nomifensin (withdrawn because of the rare occurrence of haemolysis) owed their antidepressant efficacy to their ability to increase central dopaminergic function. There are also open label studies to suggest... 

Al-Khatib IM, Fujiwara M, Ueki S (1989) Relative importance of the dopaminergic system in haloperidol-catalepsy and the anticataleptic effect of antidepressants and methamphetamine in rats. Pharmacol Biochem Behav 33 93-91. 

Garattini S. Pharmacology of amineptine, an antidepressant agent acting on the dopaminergic system a review. Int Clin Psychopharmacol 1997 12(Suppl 3) S15-9. 

COMT hypothesis. According to this hypothesis. St. John s wort increases the levels of catecholamines at the brain synapses by inhibiting their inactivation by oxidative deamination (MAOl) and by catechol functionalization (catechol-0-methyltransferase [COMTl). Recent studies have shown that hypericins possess such activities only at pharmacologically excessive concentrations. If true, these effects at normal doses are small and do nothing to alleviate depression. Other hypotheses suggest hormonal effects or effects on the dopaminergic system. Hyperforin has become a candidate for the major antidepressant constituent of St. John s wort. 

Treatment for tobacco dependence involves a combination of behavioral therapies and pharmacological treatment. The most common pharmacological treatments involve nicotine repiacement therapy (NRT) and non-nicotine medications, including antidepressants. The antidepressant with the greatest weight of evidence for efficacy in the treatment of tobacco dependence is bupropion. The efficacy of bupropion for the treatment of tobacco dependence is attributed to the blockade of dopamine reuptake in the mesolimbic dopaminergic system. This area of the brain is believed to mediate reward for nicotine use and for other drug dependences. 

Bupropion is another alternative pharmacological approach to tobacco abstinence. It is an antidepressant drug that blocks reuptake of norepinephrine and dopamine, and also blocks nicotinic receptors in the low to intermediate micromolar range (Fryer and Lukas 1999). Thus, the effects of bupropion on nicotine addiction may be through dual effects on dopaminergic and nicotinic systems. Further, it has been an effective treatment in controlled studies, both alone and in combination with the nicotine patch. Bupropion alone or in combination with a nicotine patch was more effective than placebo or the nicotine patch alone. 

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