Biomedical subjects
Publications and source records attributed to David J Nutt.
Venlafaxine represents a new class of antidepressant, the serotonin and noradrenaline re-uptake inhibitor (or SNRI). This article discusses its evolution, pharmacological properties and role in the treatment of depression and related disorders, beginning with an outline of the biology of depression.
Anxiety disorders are prevalent and associated with increased morbidity and mortality. Some chronic anxiety disorders, including generalized anxiety disorder (GAD), may be characterized by an underlying high level of anxiety on which exacerbations of symptoms are superimposed. Effective treatment of anxiety disorders should therefore strive to attain both an acute reduction in the symptoms of anxiety (a response) and sustained resolution of the symptoms of any underlying chronic anxiety (remission). This strategy may necessitate long-term treatment of these disorders by pharmacotherapy and/or psychotherapy. Studies using the serotonin and norepinephrine reuptake inhibitor (SNRI), venlafaxine extended release (XR), suggest that these aims may be achieved using this newer class of drugs. Studies with venlafaxine XR in patients with GAD have demonstrated robust anxiolytic efficacy over placebo, particularly regarding worry, cognitive dysfunction, and muscular tension, which are specific to GAD. Administration of venlafaxine XR over both short- (8-week) and long-term (6-month) periods resulted in a significantly greater number of patients achieving response and remission than obtained with placebo. Long-term treatment with venlafaxine XR in patients with GAD showed greater efficacy than that observed in short-term studies. This was achieved without any loss of short-term efficacy and patients' social functioning was also restored. While available data indicate that venlafaxine XR is an appropriate choice of agent in the long-term treatment of GAD, more studies are needed to determine how to further increase remission rates and to maintain remission beyond 6 months.
A wide range of effective drugs is available for the treatment of major depression. The discovery of these agents has not always been the result of rational drug design. Tricyclic antidepressants formed the mainstay of treatment until the 1990s, and selective serotonin reuptake inhibitors (SSRIs) have dominated treatment over the last decade. However, the poor tolerability associated with tricyclic antidepressants and concerns about the efficacy of SSRIs has led to the search for alternative agents. Attention has focused on those drugs that affect norepinephrine and/or serotonin systems, with the recent introduction of a number of agents, including venlafaxine, milnacipran, nefazodone, mirtazapine, and reboxetine. Venlafaxine, which is the first in a new class of drugs known as serotonin and norepinephrine reuptake inhibitors, may be associated with an earlier onset of action and higher remission rates than SSRIs. It is hoped that the development of drugs with multiple sites of action will translate into improved clinical efficacy in the treatment of depression.
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Two enantiomers IR, 2S-(+)-cis (3a) and IS, 2R-(-)-cis (3b) of 1-[(4,5-dihydroimidazolidin-2-yl)imino]indan-2-ol were prepared by reacting 2-chloro-4,5-dihydroimidazole (1) with corresponding 1-amino-indan-2-ols (2a-b). The compounds obtained are structural analogues of PMS 952 agent containing imino bridge in place of methylene group. Compound 3a exhibited moderate almost equal activity at both imidazoline I2 receptors and alpha2-adrenoceptors, while enantiomer 3b was found to be selective for alpha2-adrenoceptors (alpha2/I2 selectivity ratio = 10.4).