The Experts below are selected from a list of 2163 Experts worldwide ranked by ideXlab platform
Stephen M Stahl - One of the best experts on this subject based on the ideXlab platform.
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vilazodone a brief pharmacological and clinical review of the novel serotonin partial agonist and reuptake inhibitor
Therapeutic Advances in Psychopharmacology, 2011Co-Authors: Thomas L Schwartz, Umar A Siddiqui, Stephen M StahlAbstract:Background: Vilazodone is the latest US Food and Drug Administration approved Antidepressant Agent available in the USA. Its putative mechanism of Antidepressant action enhances the release of sero...
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effectiveness of ipsapirone a 5 ht 1a partial agonist in major depressive disorder support for the role of 5 ht 1a receptors in the mechanism of action of serotonergic Antidepressants
The International Journal of Neuropsychopharmacology, 1998Co-Authors: Stephen M Stahl, Lee Kaiser, Julie Roeschen, Jan Keppel M Hesselink, John OrazemAbstract:Desensitisation of serotonin 1A (5-HT-1A) receptors is a leading hypothesis for the mechanism of action of Antidepressants which block serotonin reuptake. This hypothesis predicts that direct-acting 5-HT-1A agonists should also exhibit anti-depressant properties. Here we report the results of the first large-scale controlled study of the efficacy and tolerability of a 5-HT-1A agonist in outpatients with major depressive disorder (MDD). Three hundred and seventy-three subjects meeting DSM-III-R criteria for MDD participated in this randomised, double-blind comparison of the 5-HT-1A partial agonist ipsapirone (5 mg, 7.5 mg and 10 mg t.i.d.) to placebo t.i.d. Improvement in depressive symptoms relative to placebo, as measured by the Hamilton Depression Rating Scale, occurred in the ipsapirone (7.5 mg t.i.d.) group with a magnitude of effect (D=-2.53 points) that was statistically significant (p=0.010). Adverse events occurred in 76% of the placebo patients and 92% of the ipsapirone patients. A dose-related increase in the incidence of adverse events led to discontinuation of treatment with the 10 mg t.i.d. Results of this study demonstrate that ipsapirone, at a dose of 7.5 mg t.i.d., is an effective Antidepressant Agent in the treatment of MDD, supporting the hypothesised role of 5-HT-1A receptors in the mechanism of action of serotonin reuptake inhibitors. However, as a potential therapeutic Agent for depression, ipsapirone shows only a modest magnitude of drug-placebo differences as well as a side-effect profile less favorable than many of the newer Antidepressants.
John Orazem - One of the best experts on this subject based on the ideXlab platform.
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effectiveness of ipsapirone a 5 ht 1a partial agonist in major depressive disorder support for the role of 5 ht 1a receptors in the mechanism of action of serotonergic Antidepressants
The International Journal of Neuropsychopharmacology, 1998Co-Authors: Stephen M Stahl, Lee Kaiser, Julie Roeschen, Jan Keppel M Hesselink, John OrazemAbstract:Desensitisation of serotonin 1A (5-HT-1A) receptors is a leading hypothesis for the mechanism of action of Antidepressants which block serotonin reuptake. This hypothesis predicts that direct-acting 5-HT-1A agonists should also exhibit anti-depressant properties. Here we report the results of the first large-scale controlled study of the efficacy and tolerability of a 5-HT-1A agonist in outpatients with major depressive disorder (MDD). Three hundred and seventy-three subjects meeting DSM-III-R criteria for MDD participated in this randomised, double-blind comparison of the 5-HT-1A partial agonist ipsapirone (5 mg, 7.5 mg and 10 mg t.i.d.) to placebo t.i.d. Improvement in depressive symptoms relative to placebo, as measured by the Hamilton Depression Rating Scale, occurred in the ipsapirone (7.5 mg t.i.d.) group with a magnitude of effect (D=-2.53 points) that was statistically significant (p=0.010). Adverse events occurred in 76% of the placebo patients and 92% of the ipsapirone patients. A dose-related increase in the incidence of adverse events led to discontinuation of treatment with the 10 mg t.i.d. Results of this study demonstrate that ipsapirone, at a dose of 7.5 mg t.i.d., is an effective Antidepressant Agent in the treatment of MDD, supporting the hypothesised role of 5-HT-1A receptors in the mechanism of action of serotonin reuptake inhibitors. However, as a potential therapeutic Agent for depression, ipsapirone shows only a modest magnitude of drug-placebo differences as well as a side-effect profile less favorable than many of the newer Antidepressants.
D Bradford - One of the best experts on this subject based on the ideXlab platform.
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an open study of oral flesinoxan a 5 ht1a receptor agonist in treatment resistant depression
International Clinical Psychopharmacology, 1993Co-Authors: P Grof, R Joffe, Sidney H Kennedy, E Persad, J Syrotiuk, D BradfordAbstract:Flesinoxan, a full 5-HT1A receptor agonist, was administered (4-8 mg) to treatment-resistant depressed patients in an open study. Safety and tolerance of the substance appeared satisfactory. Headache, dizziness and nausea were the most frequently reported side effects. The observations suggested that flesinoxan is an Antidepressant Agent and that it may be of particular value in some difficult, treatment-resistant depressions. Based on these observations, a double-blind, placebo-controlled evaluation of flesinoxan's efficacy appears warranted.
Mark J Millan - One of the best experts on this subject based on the ideXlab platform.
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anxiolytic properties of agomelatine an Antidepressant with melatoninergic and serotonergic properties role of 5 ht2c receptor blockade
Psychopharmacology, 2005Co-Authors: Mark J Millan, Alain P. Gobert, Mauricette Brocco, Anne DekeyneAbstract:Rationale The novel Antidepressant Agent, agomelatine, behaves as an agonist at melatonin receptors and as an antagonist at serotonin (5-HT)2C receptors.
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differential modulation of efficiency in a food rewarded differential reinforcement of low rate 72 s schedule in rats by norepinephrine and serotonin reuptake inhibitors
Psychopharmacology, 2002Co-Authors: Anne Dekeyne, Alain P. Gobert, Agnes L Auclair, Sylvie Girardon, Mark J MillanAbstract:Abstract Rationale. The differential reinforcement of low-rate 72-s (DRL 72-s) schedule, in which rats must withhold a response for at least 72 s to obtain a reward (generally water), is an attractive procedure for the characterisation of potential Antidepressant Agents. Indeed, several Antidepressants have been shown to improve efficiency (ratio of reinforcement rate to response rate) in this model, either by decreasing response rates and/or by increasing reinforcement rates. Objective. Herein, we compared the actions of Antidepressants known to inhibit serotonin (5-HT), norepinephrine (NE) and/or dopamine (DA) reuptake in a food-rewarded DRL 72-s schedule. Methods. Rats trained in a food-rewarded DRL 72-s schedule and showing stable baseline performance were administered with drugs i.p. once a week. In independent experiments, the influence of drugs on food intake, spontaneous locomotor activity and extracellular levels of monoamines in the frontal cortex was evaluated. Results. In confirmation of previous studies, the tricyclic Agent imipramine (10.0 mg/kg) and the "atypical" Agent mianserin (40.0 mg/kg) significantly increased efficiency. In analogy, the selective NE reuptake inhibitors (NARIs) desipramine (20.0 mg/kg), nortriptyline (2.5 mg/kg) and reboxetine (0.63 mg/kg) all displayed marked enhancements in efficiency. In contrast, the selective 5-HT reuptake inhibitors (SSRIs) citalopram (10.0 mg/kg), fluvoxamine (10.0 mg/kg) and paroxetine (10.0 mg/kg) all significantly decreased efficiency. The mixed 5-HT/NE reuptake inhibitors (SNRIs) venlafaxine (2.5 mg/kg, 10.0 mg/kg) and S33005 (0.16–10.0 mg/kg), likewise, did not increase efficiency. Further, the DA reuptake inhibitors (DARIs) bupropion (0.16–10.0 mg/kg) and GBR12935 (0.63–10.0 mg/kg) had no effect on DRL 72-s performance. All drug classes exerted a similar, mild inhibitory influence on food intake and locomotor behaviour. Imipramine, mianserin and NARIs markedly increased extracellular levels of NE, and SSRIs elevated levels of 5-HT, while SSRIs augmented levels of both. Conclusions. The present experimental procedure demonstrates, in analogy to imipramine and mianserin, robust and consistent increases in efficiency with NARIs. Their effects may be distinguished from a decrease in efficiency elicited by SSRIs, and a lack of activity of SNRIs and DARIs. While the reasons underlying the ineffectiveness of SSRIs (in contrast to previous studies) remain to be clarified, these data underline the importance of adrenergic mechanisms in the control of behaviour under conditions of delayed responding. Further, they support the interest of DRL 72-s procedures for the characterisation of diverse classes of Antidepressant Agent.
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Reciprocal autoreceptor and heteroreceptor control of serotonergic, dopaminergic and noradrenergic transmission in the frontal cortex: relevance to the actions of Antidepressant Agents.
Journal of psychopharmacology (Oxford England), 2000Co-Authors: Mark J Millan, Françoise Lejeune, Alain P. GobertAbstract:The frontal cortex (FCX) plays a key role in processes that control mood, cognition and motor behaviour, functions which are compromised in depression, schizophrenia and other psychiatric disorders. In this regard, there is considerable evidence that a perturbation of monoaminergic input to the FCX is involved in the pathogenesis of these states. Correspondingly, the modulation of monoaminergic transmission in the FCX and other corticolimbic structures plays an important role in the actions of antipsychotic and Antidepressant Agents. In order to further understand the significance of monoaminergic systems in psychiatric disorders and their treatment, it is essential to characterize mechanisms underlying their modulation. Within this framework, the present commentary focuses on our electrophysiological and dialysis analyses of the complex and reciprocal pattern of auto- and heteroreceptor mediated control of dopaminergic, noradrenergic and serotonergic transmission in the FCX. The delineation of such interactions provides a framework for an interpretation of the influence of diverse classes of Antidepressant Agent upon extracellular levels of dopamine, noradrenaline and serotonin in FCX. Moreover, it also generates important insights into strategies for the potential improvement in the therapeutic profiles of Antidepressant Agents.
Anne Dekeyne - One of the best experts on this subject based on the ideXlab platform.
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anxiolytic properties of agomelatine an Antidepressant with melatoninergic and serotonergic properties role of 5 ht2c receptor blockade
Psychopharmacology, 2005Co-Authors: Mark J Millan, Alain P. Gobert, Mauricette Brocco, Anne DekeyneAbstract:Rationale The novel Antidepressant Agent, agomelatine, behaves as an agonist at melatonin receptors and as an antagonist at serotonin (5-HT)2C receptors.
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differential modulation of efficiency in a food rewarded differential reinforcement of low rate 72 s schedule in rats by norepinephrine and serotonin reuptake inhibitors
Psychopharmacology, 2002Co-Authors: Anne Dekeyne, Alain P. Gobert, Agnes L Auclair, Sylvie Girardon, Mark J MillanAbstract:Abstract Rationale. The differential reinforcement of low-rate 72-s (DRL 72-s) schedule, in which rats must withhold a response for at least 72 s to obtain a reward (generally water), is an attractive procedure for the characterisation of potential Antidepressant Agents. Indeed, several Antidepressants have been shown to improve efficiency (ratio of reinforcement rate to response rate) in this model, either by decreasing response rates and/or by increasing reinforcement rates. Objective. Herein, we compared the actions of Antidepressants known to inhibit serotonin (5-HT), norepinephrine (NE) and/or dopamine (DA) reuptake in a food-rewarded DRL 72-s schedule. Methods. Rats trained in a food-rewarded DRL 72-s schedule and showing stable baseline performance were administered with drugs i.p. once a week. In independent experiments, the influence of drugs on food intake, spontaneous locomotor activity and extracellular levels of monoamines in the frontal cortex was evaluated. Results. In confirmation of previous studies, the tricyclic Agent imipramine (10.0 mg/kg) and the "atypical" Agent mianserin (40.0 mg/kg) significantly increased efficiency. In analogy, the selective NE reuptake inhibitors (NARIs) desipramine (20.0 mg/kg), nortriptyline (2.5 mg/kg) and reboxetine (0.63 mg/kg) all displayed marked enhancements in efficiency. In contrast, the selective 5-HT reuptake inhibitors (SSRIs) citalopram (10.0 mg/kg), fluvoxamine (10.0 mg/kg) and paroxetine (10.0 mg/kg) all significantly decreased efficiency. The mixed 5-HT/NE reuptake inhibitors (SNRIs) venlafaxine (2.5 mg/kg, 10.0 mg/kg) and S33005 (0.16–10.0 mg/kg), likewise, did not increase efficiency. Further, the DA reuptake inhibitors (DARIs) bupropion (0.16–10.0 mg/kg) and GBR12935 (0.63–10.0 mg/kg) had no effect on DRL 72-s performance. All drug classes exerted a similar, mild inhibitory influence on food intake and locomotor behaviour. Imipramine, mianserin and NARIs markedly increased extracellular levels of NE, and SSRIs elevated levels of 5-HT, while SSRIs augmented levels of both. Conclusions. The present experimental procedure demonstrates, in analogy to imipramine and mianserin, robust and consistent increases in efficiency with NARIs. Their effects may be distinguished from a decrease in efficiency elicited by SSRIs, and a lack of activity of SNRIs and DARIs. While the reasons underlying the ineffectiveness of SSRIs (in contrast to previous studies) remain to be clarified, these data underline the importance of adrenergic mechanisms in the control of behaviour under conditions of delayed responding. Further, they support the interest of DRL 72-s procedures for the characterisation of diverse classes of Antidepressant Agent.