Anxiety Disorders: Moret C

Stahl SM, Grady MM, Moret C, Briley M. · Department of Psychiatry, University of California, San Diego, San Diego, CA, USA. · CNS Spectr. · Pubmed #16142213 links to  free full text

Abstract: The class of serotonin and norepinephrine reuptake inhibitors (SNRIs) now comprises three medications: venlafaxine, milnacipran, and duloxetine. These drugs block the reuptake of both serotonin (5-HT) and norepinephrine with differing selectivity. Whereas milnacipran blocks 5-HT and norepinephrine reuptake with equal affinity, duloxetine has a 10-fold selectivity for 5-HT and venlafaxine a 30-fold selectivity for 5-HT. All three SNRIs are efficacious in treating a variety of anxiety disorders. There is no evidence for major differences between SNRIs and SSRIs in their efficacy in treating anxiety disorders. In contrast to SSRIs, which are generally ineffective in treating chronic pain, all three SNRIs seem to be helpful in relieving chronic pain associated with and independent of depression. Tolerability of an SNRI at therapeutic doses varies within the class. Although no direct comparative data are available, venlafaxine seems to be the least well-tolerated, combining serotonergic adverse effects (nausea, sexual dysfunction, withdrawal problems) with a dose-dependent cardiovascular phenomenon, principally hypertension. Duloxetine and milnacipran appear better tolerated and essentially devoid of cardiovascular toxicity.

Briley M, Moret C. · NeuroBiz Consulting and Communications, Les Grèzes, La Verdarié, 81100 Castres, France. · IDrugs. · Pubmed #12861471 No free full text.

Abstract: Fibromyalgia syndrome (FMS) is a chronic disease of widespread and debilitating pain. The cause of FMS is unknown and its risk factors are poorly understood. It occurs frequently in the general population where it is often co-morbid with other rheumatoid and pain disorders, and psychiatric disorders such as anxiety and depression, making diagnosis particularly difficult. Several types of drugs are used to treat FMS, but none are specifically approved for this indication. FMS appears to be strongly associated with depression or at least with some symptoms of depression, and antidepressants appear to be effective in the treatment of this disorder. The advent of new classes of antidepressants with fewer side effects than older drugs has suggested new avenues of therapy for patients diagnosed with FMS.

Moret C, Grimaldi B, Massot O, Fillion G. · NeuroBiz Consulting and Communications, Castres, France. · Semin Clin Neuropsychiatry. · Pubmed #12728412 No free full text.

Abstract: The endogenous neuropeptide, 5-HT-moduline, selectively and allosterically interacts with 5-HT(1B) receptors. By binding at a site distinct from that bound by 5-HT, 5-HT-moduline induces structural changes in 5-HT(1B) receptors or stabilizes a particular conformation of these receptors. These conformational changes ultimately lead to the prevention of 5-HT binding resulting in desensitization of these receptors and reduction of the serotonergic function. The efficacy of 5-HT(1B) receptor agonists, for example, has been shown to be reduced by this peptide in vitro and behaviorally. In addition, 5-HT-moduline increases 5-HT release, which is regulated by presynaptic 5-HT(1B) autoreceptors. The release of 5-HT-moduline itself is increased after acute restraint stress in rats, whereas deactivation of 5-HT-moduline by specific antibodies in mice prevents the development of anxiety in a classic behavioral model, suggesting a potential role of the peptide in the control of anxiety. It is thus hypothesized that agents inhibiting the effect of 5-HT-moduline could have anxiolytic activity. Because the serotonergic activity is known to play a key role in psychiatric disorders such as depression and anxiety, compounds capable of mimicking or inhibiting the activity of 5-HT-moduline can represent novel antidepressants or anxiolytics.

Moret C, Briley M. · NeuroBiz BioConsulting, Les Grèzes, La Verdarié, 81100, Castres, France. · Eur J Pharmacol. · Pubmed #10980257 No free full text.

Abstract: Serotonin (5-hydroxytryptamine, 5-HT) is implicated in several psychiatric diseases. Is this also true for 5-HT(1B/D) receptors? These receptors are found in high density in substantia nigra, globus pallidus, striatum and basal ganglia and in other brain regions. This ubiquity makes 5-HT(1B/D) receptors responsible for many physiological and behavioural functions. This review focuses on the role of 5-HT(1B) receptors in the regulation of 5-HT release and synthesis. Microdialysis experiments performed on freely moving animals are an interesting in vivo model to study the function of the terminal 5-HT(1B) autoreceptor. Synthesis of 5-HT, estimated by the measurement of the accumulation of 5-hydroxytryptophan (5-HTP) ex vivo or in vitro, is modulated by the 5-HT(1B) autoreceptors. Many reports have shown that chronic administration with selective serotonin reuptake inhibitors leads to the desensitisation of the terminal 5-HT(1B) autoreceptors. With the help of some animal models of depression and anxiety and with some data from clinical studies it has been hypothesised that 5-HT(1B) receptors may be supersensitive in depression, anxiety and obsessive compulsive disorder. Thus, since the dysfunction of 5-HT(1B) receptors may be involved in some pathological states, particularly in the psychiatric field, these receptors represent important potential targets for drugs to treat mental diseases.

Moret C, Briley M. · NeuroBiz Consulting & Communications, Les Grèzes, La Verdarié, 81100 Castres, France. · Neuropsychiatr Dis Treat. · Pubmed #19412502 links to  free full text

Abstract: Fibromyalgia syndrome is a chronic disease of widespread and debilitating pain whose cause is unknown and whose risk factors are poorly understood. It is often comorbid with rheumatoid and other pain disorders as well as psychiatric disorders such as anxiety and depression. Although they are not officially approved for this indication, antiepileptics and antidepressants are often used to treat fibromyalgia. The tricyclic antidepressants (TCAs), particularly amitriptyline, are among the most common treatment strategies. Because of the poor tolerability of the tricyclics, the newer antidepressants have been widely tested in fibromyalgia. The selective serotonin reuptake inhibitors (SSRIs) and the reversible monoamine oxidase inhibitors do not seem to be particularly helpful. The serotonin and norepinephrine reuptake inhibitors (SNRIs), duloxetine and milnacipran, on the other hand, have been shown in placebo-controlled trials to offer significant relief to patients suffering from fibromyalgia. Although no direct comparative studies have been performed, these compounds appear to be as effective as the TCAs but much better tolerated. The effectiveness of the SNRIs as well as other dual acting antidepressants, such as mirtazapine, but not the SSRIs, implies that a dysfunction of both serotonin and norepinephrine neurotransmission probably exists in fibromyalgia. The effectiveness of antidepressants appears to be independent of their effect on comorbid depression.

Moret C, Briley M. · NeuroBiz Consulting & Communications, Les Grèzes, La Verdarié, 81100 Castres, France. · IDrugs. · Pubmed #15965850 No free full text.

Abstract: The benzodiazepines have monopolized the acute anxiety market for about 40 years, but their potential for tolerance and dependency has stimulated an interest in alternative anxiolytics. Until recently, however, attention has focused on existing drugs such as monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors. The 5-HT1A partial agonist, buspirone (Bristol-Myers-Squibb), is one of the few compounds developed principally as an anxiolytic since the benzodiazepines. The challenge for the future is not only to find efficacious treatments with a rapid onset of action and an acceptable side effect profile but also to determine the optimal compounds for each of the different anxiety disorders.