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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by SLS on November 3, 2009, at 17:29:45
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Curr Drug Targets. 2009 Nov 1. [Epub ahead of print]
Therapeutic Potential of 5-HT(7) Receptors in Mood Disorders.Mnie-Filali O, Lambas-Señas L, Scarna H, Haddjeri N.
Université de Lyon, F-69373, Lyon, France; Université Lyon 1, ISPB, Laboratoire de Neuropharmacologie, Lyon, France; CNRS, EAC 5006, France. [email protected].
Serotonin (5-HT) exerts its diverse physiological and pharmacological effects through the activation of multiple receptor subtypes. One of the newest members of this family is the 5-HT(7) receptor. Increasing investigations on this receptor are currently undertaken to highlight its physiological and physiopathological significance. With the development of selective 5-HT(7) receptor ligands, preclinical studies have started to elucidate the functions of this receptor subtype in more details. Hence, growing body of evidence suggests that the 5-HT(7) receptor is involved in biological processes such as circadian rhythm and thermoregulation, in addition to disorders in which disturbances of the latter are considered to be an important contributing factor. Moreover, preclinical data support the use of 5-HT(7) receptor antagonism as a promising mechanism for the treatment of several dysfunctions such as cognitive deficits and, importantly, have also unveiled anxiolytic and antidepressant-like properties. In this review, we will report major advances in the discovery of 5-HT(7) receptor roles, with special emphasis on the potential application of their antagonists as novel anxiolytic and antidepressant drugs.
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- Scott
Posted by metafunj on November 3, 2009, at 20:21:16
In reply to 5-HT7 Receptors in Mood Disorders - New Hope?, posted by SLS on November 3, 2009, at 17:29:45
I believe mianiserin is an 5 HT 7 receptor antagonist. For some reason Mirtazapine has never been tested as to whether it antagonizes this receptor, but I read that it is possible that it does.
Posted by brot on November 6, 2009, at 11:09:04
In reply to Re: 5-HT7 Receptors in Mood Disorders - New Hope? » SLS, posted by metafunj on November 3, 2009, at 20:21:16
Psychopharmacology (Berl). 2009 Jul;205(1):119-28. Epub 2009 Apr 1.
Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo.Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL.
Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
RATIONALE: Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy. Amisulpride has also been demonstrated to be an antidepressant for patients with major depression in many clinical trials. In part because of the selective D(2)/D(3) receptor antagonist properties of amisulpride, it has long been widely assumed that dopaminergic modulation is the proximal event responsible for mediating its antidepressant and antipsychotic properties. OBJECTIVES: The purpose of these studies was to determine if amisulpride's antidepressant actions are mediated by off-target interactions with other receptors. MATERIALS AND METHODS: We performed experiments that: (1) examined the pharmacological profile of amisulpride at a large number of central nervous system (CNS) molecular targets and, (2) after finding high potency antagonist affinity for human 5-HT(7a) serotonin receptors, characterized the actions of amisulpride as an antidepressant in wild-type and 5-HT(7) receptor knockout mice. RESULTS: We discovered that amisulpride was a potent competitive antagonist at 5-HT(7a) receptors and that interactions with no other molecular target investigated in this paper could explain its antidepressant actions in vivo. Significantly, and in contrast to their wild-type littermates, 5-HT(7) receptor knockout mice did not respond to amisulpride in two widely used rodent models of depression, the tail suspension test and the forced swim test. CONCLUSIONS: These results indicate that 5-HT(7a) receptor antagonism, and not D(2)/D(3) receptor antagonism, likely underlies the antidepressant actions of amisulpride.
PMID: 19337725 [PubMed - indexed for MEDLINE]
Posted by metafunj on November 6, 2009, at 16:26:51
In reply to Re: 5-HT7 Receptors in Mood Disorders - New Hope?, posted by brot on November 6, 2009, at 11:09:04
nice find there, bread.
Posted by mtdewcmu on January 2, 2010, at 22:09:45
In reply to Re: 5-HT7 Receptors in Mood Disorders - New Hope?, posted by brot on November 6, 2009, at 11:09:04
> Psychopharmacology (Berl). 2009 Jul;205(1):119-28. Epub 2009 Apr 1.
> Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo.
>
> Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL.
>
> Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
>
> RATIONALE: Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy. Amisulpride has also been demonstrated to be an antidepressant for patients with major depression in many clinical trials. In part because of the selective D(2)/D(3) receptor antagonist properties of amisulpride, it has long been widely assumed that dopaminergic modulation is the proximal event responsible for mediating its antidepressant and antipsychotic properties. OBJECTIVES: The purpose of these studies was to determine if amisulpride's antidepressant actions are mediated by off-target interactions with other receptors. MATERIALS AND METHODS: We performed experiments that: (1) examined the pharmacological profile of amisulpride at a large number of central nervous system (CNS) molecular targets and, (2) after finding high potency antagonist affinity for human 5-HT(7a) serotonin receptors, characterized the actions of amisulpride as an antidepressant in wild-type and 5-HT(7) receptor knockout mice. RESULTS: We discovered that amisulpride was a potent competitive antagonist at 5-HT(7a) receptors and that interactions with no other molecular target investigated in this paper could explain its antidepressant actions in vivo. Significantly, and in contrast to their wild-type littermates, 5-HT(7) receptor knockout mice did not respond to amisulpride in two widely used rodent models of depression, the tail suspension test and the forced swim test. CONCLUSIONS: These results indicate that 5-HT(7a) receptor antagonism, and not D(2)/D(3) receptor antagonism, likely underlies the antidepressant actions of amisulpride.
>
> PMID: 19337725 [PubMed - indexed for MEDLINE]That suggests that using antipsychotics as antidepressants is needlessly exposing people to the complications of dopamine antagonism. Unfortunately, it will be years before we get any new drugs based on research happening now.
Posted by SLS on January 3, 2010, at 7:19:07
In reply to Re: 5-HT7 Receptors in Mood Disorders - New Hope?, posted by mtdewcmu on January 2, 2010, at 22:09:45
They don't mention that as a ligand, amisulpride is preferential for presynaptic receptors at low dosages. That this might produce an increase in the synthesis and release of dopamine without significant postsynaptic receptor blockade might contribute to its antidepressant properties.
- Scott
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