ISBN : 978-93-85073-24-3 5-HT, 5-hydroxytryptamine (serotonin); AMI, amitriptyline; DMI, desipramine; IMI, imipramine; MAOI, monoamine oxidase inhibitor; NE, norepinephrine; NT, nortriptyline; SNRI, selective norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. In the fourth and final heterogeneous group are drugs without known potent, acute pharmacologic effects that result in enhancement of noradrenergic or serotoninergic transmission. In other words, their mechanisms of action are unknown. Drugs in this category include the TCA trimipramine and also bupropion, nefazodone, and trazodone. It has been speculated that bupropion acts through dopaminergic mechanisms because it is the only antidepressant that more potently blocks the reuptake of dopamine than that of either NE or 5-HT [114]. The brain is one of the most important organs of the human body, if not the most, and its homeostasis is of primary importance. In fact, specific interfaces also referred to as barriers; tightly regulate the exchange between the peripheral blood circulation and the cerebrospinal fluid (CSF) circulatory system. These barriers are represented by the choroids plexus (CP) epithelium (blood-ventricular CSF), the arachnoid epithelium (blood-subarachnoid CSF), and the BBB (blood-brain barrier interstitial fluid) [115]. The blood-brain barrier (BBB) (Fig 1.2) is the bottleneck in brain drug development and is the single most important factor limiting the future growth of neurotherapeutics [116]. 7
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