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A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), more commonly known as a triple reuptake inhibitor (TRI), is a drug that concomitantly acts as a reuptake inhibitor for the monoamine neurotransmitters serotonin (5-HT), norepinephrine (noradrenaline, NA) and dopamine (DA), by blocking the action of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. This, in turn, increases extracellular concentrations of these neurotransmitters and, therefore, an increase in serotonergic, noradrenergic or adrenergic, and dopaminergic neurotransmission. This group of drugs works in a way similar to the monoamine ''releasers'' (e.g., PAL-303, PAL-287), albeit through different mechanism (read reviews by R. Rothman et al.). Nonselective MAOIs, including tranylcypromine and phenelzine also elevate the extracellular concentration of monoaminergic neurotransmitters (i.e. 5-HT, NA and DA) in the CNS. Many of the substituted amphetamines also display MAOI activity, although they are reversible and not 'suicide inhibitors' (alkylating agents that can form a covalent bond/s with their molecular targets). Note: alkylating agents that can penetrate the CNS have been used as antineoplastics (c.f. cyclomustine and procarbazine). Such compounds are often (somewhat disparagingly) referred to as 'dirty drugs' (not because low chemical purity of the compounds though); because they recruit a plurality of modes of activity. Bryan Roth used the term selectively–nonselective;.〔〔 ==Depression== Major depressive disorder (MDD) is the foremost reason supporting the need for development of an SNDRI. According to the World Health Organization, depression is the leading cause of disability and the 4th leading contributor to the global burden of disease in 2000. By the year 2020, depression is projected to reach 2nd place in the ranking of DALYs. About 16% of the population is estimated to be affected by major depression, and another 1% is affected by bipolar disorder.In both cases, during one or more times throughout an individual's lifetime. The presence of the common symptoms of these disorders are collectively called 'depressive syndrome' and includes a long-lasting depressed mood, feelings of guilt, anxiety, and recurrent thoughts of death and suicide. Other symptoms including poor concentration, a disturbance of sleep rhythms (insomnia or hypersomnia), and severe fatigue may also occur. Individual patients present differing subsets of symptoms, which may change over the course of the disease highlighting its multifaceted and heterogeneous nature.〔 Depression is often highly comorbid with other diseases, e.g. cardiovascular disease (myocardial infarction, stroke),〔 diabetes, cancer, Depressed subjects are prone to smoking, substance abuse, eating disorders, obesity, high blood pressure, pathological gambling and internet addiction, and on average have a 15 to 30 year shorter lifetime compared with the general population. Major depression can strike at virtually any time of life as a function of genetic and developmental pre-disposition in interaction with adverse life-events. Although common in the elderly, over the course of the last century, the average age for a first episode has fallen to ~30 years. However, depressive states (with subtly different characteristics) are now frequently identified in adolescents and even children. The differential diagnosis (and management) of depression in young populations requires considerable care and experience; for example, apparent depression in teenagers may later transpire to represent a prodromal phase of schizophrenia.〔 The ability to work, familial relationships, social integration, and self-care are all severely disrupted.〔 The genetic contribution has been estimated as 40-50%. However, combinations of multiple genetic factors may be involved because a defect in a single gene usually fails to induce the multifaceted symptoms of depression.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Serotonin–norepinephrine–dopamine reuptake inhibitor」の詳細全文を読む スポンサード リンク
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