WAY-163909, a 5-HT2C agonist, enhances the preclinical potency of current antipsychotics.
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| Title: | WAY-163909, a 5-HT |
|---|---|
| Authors: | Grauer, Steven, Graf, Radka, Navarra, Rachel, Sung, Amy, Logue, Sheree, Stack, Gary, Huselton, Christine, Liu, Zhi, Comery, Thomas, Marquis, Karen, Rosenzweig-Lipson, Sharon |
| Source: | Psychopharmacology. May2009, Vol. 204 Issue 1, p37-48. 12p. 3 Charts, 7 Graphs. |
| Subjects: | Antipsychotic agents, Dopamine, Catecholamines, Neurotransmitters, Dopamine agonists |
| Abstract: | 5-HT2C agonists, by decreasing mesolimbic dopamine without affecting nigrostriatal dopamine, are predicted to have antipsychotic efficacy with low extrapyramidal side effects (EPS). Combining 5-HT2C agonists with low doses of existing antipsychotics could increase treatment efficacy while reducing treatment liabilities such as EPS (typical antipsychotics), and the propensity for weight gain (atypical antipsychotics). The objectives of these studies were to combine WAY-163909, a selective 5-HT2C agonist, with either the typical antipsychotic haloperidol, or the atypical antipsychotic clozapine, at doses that were ineffective on their own, with the expectation that a shift in potency in several rodent behavior models predictive of antipsychotic activity would occur. In mice, co-administration of either haloperidol, or clozapine, produced a significant leftward shift in the ability of WAY-163909 to block apomorphine-induced climbing behavior, without any affect on apomorphine-induced stereotypy or an increased propensity for catalepsy. In the rat-conditioned avoidance model, WAY-163909 was combined with either haloperidol or clozapine at doses that individually produced reductions in avoidance response on the order of 10%, while the combination of WAY-163909 and either of the antipsychotics resulted in a greater than 70% reduction in avoidance, with no evidence of response failures, or pharmacokinetic interaction. Doses of either haloperidol or clozapine, that failed to antagonize an MK-801 induced deficit in prepulse inhibition, significantly attenuated the sensory gating deficit when combined with WAY-163909. Data support the notion that 5-HT2C receptor agonists, co-administered with other marketed antipsychotics, allow for dose sparing with a more favorable side-effect profile. [ABSTRACT FROM AUTHOR] |
| Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 37826523 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: WAY-163909, a 5-HT<subscript>2C</subscript> agonist, enhances the preclinical potency of current antipsychotics. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Grauer%2C+Steven%22">Grauer, Steven</searchLink><br /><searchLink fieldCode="AR" term="%22Graf%2C+Radka%22">Graf, Radka</searchLink><br /><searchLink fieldCode="AR" term="%22Navarra%2C+Rachel%22">Navarra, Rachel</searchLink><br /><searchLink fieldCode="AR" term="%22Sung%2C+Amy%22">Sung, Amy</searchLink><br /><searchLink fieldCode="AR" term="%22Logue%2C+Sheree%22">Logue, Sheree</searchLink><br /><searchLink fieldCode="AR" term="%22Stack%2C+Gary%22">Stack, Gary</searchLink><br /><searchLink fieldCode="AR" term="%22Huselton%2C+Christine%22">Huselton, Christine</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Zhi%22">Liu, Zhi</searchLink><br /><searchLink fieldCode="AR" term="%22Comery%2C+Thomas%22">Comery, Thomas</searchLink><br /><searchLink fieldCode="AR" term="%22Marquis%2C+Karen%22">Marquis, Karen</searchLink><br /><searchLink fieldCode="AR" term="%22Rosenzweig-Lipson%2C+Sharon%22">Rosenzweig-Lipson, Sharon</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. May2009, Vol. 204 Issue 1, p37-48. 12p. 3 Charts, 7 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Antipsychotic+agents%22">Antipsychotic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Dopamine%22">Dopamine</searchLink><br /><searchLink fieldCode="DE" term="%22Catecholamines%22">Catecholamines</searchLink><br /><searchLink fieldCode="DE" term="%22Neurotransmitters%22">Neurotransmitters</searchLink><br /><searchLink fieldCode="DE" term="%22Dopamine+agonists%22">Dopamine agonists</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 5-HT2C agonists, by decreasing mesolimbic dopamine without affecting nigrostriatal dopamine, are predicted to have antipsychotic efficacy with low extrapyramidal side effects (EPS). Combining 5-HT2C agonists with low doses of existing antipsychotics could increase treatment efficacy while reducing treatment liabilities such as EPS (typical antipsychotics), and the propensity for weight gain (atypical antipsychotics). The objectives of these studies were to combine WAY-163909, a selective 5-HT2C agonist, with either the typical antipsychotic haloperidol, or the atypical antipsychotic clozapine, at doses that were ineffective on their own, with the expectation that a shift in potency in several rodent behavior models predictive of antipsychotic activity would occur. In mice, co-administration of either haloperidol, or clozapine, produced a significant leftward shift in the ability of WAY-163909 to block apomorphine-induced climbing behavior, without any affect on apomorphine-induced stereotypy or an increased propensity for catalepsy. In the rat-conditioned avoidance model, WAY-163909 was combined with either haloperidol or clozapine at doses that individually produced reductions in avoidance response on the order of 10%, while the combination of WAY-163909 and either of the antipsychotics resulted in a greater than 70% reduction in avoidance, with no evidence of response failures, or pharmacokinetic interaction. Doses of either haloperidol or clozapine, that failed to antagonize an MK-801 induced deficit in prepulse inhibition, significantly attenuated the sensory gating deficit when combined with WAY-163909. Data support the notion that 5-HT2C receptor agonists, co-administered with other marketed antipsychotics, allow for dose sparing with a more favorable side-effect profile. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1007/s00213-008-1433-z Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 37 Subjects: – SubjectFull: Antipsychotic agents Type: general – SubjectFull: Dopamine Type: general – SubjectFull: Catecholamines Type: general – SubjectFull: Neurotransmitters Type: general – SubjectFull: Dopamine agonists Type: general Titles: – TitleFull: WAY-163909, a 5-HT2C agonist, enhances the preclinical potency of current antipsychotics. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Grauer, Steven – PersonEntity: Name: NameFull: Graf, Radka – PersonEntity: Name: NameFull: Navarra, Rachel – PersonEntity: Name: NameFull: Sung, Amy – PersonEntity: Name: NameFull: Logue, Sheree – PersonEntity: Name: NameFull: Stack, Gary – PersonEntity: Name: NameFull: Huselton, Christine – PersonEntity: Name: NameFull: Liu, Zhi – PersonEntity: Name: NameFull: Comery, Thomas – PersonEntity: Name: NameFull: Marquis, Karen – PersonEntity: Name: NameFull: Rosenzweig-Lipson, Sharon IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 05 Text: May2009 Type: published Y: 2009 Identifiers: – Type: issn-print Value: 00333158 Numbering: – Type: volume Value: 204 – Type: issue Value: 1 Titles: – TitleFull: Psychopharmacology Type: main |
| ResultId | 1 |
