Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia.

Article Details

Citation

Copy to clipboard

Rotella DP, McFarlane GR, Greenfield A, Grosanu C, Robichaud AJ, Denny RA, Feenstra RW, Nunez-Garcia S, Reinders JH, Neut Mv, McCreary A, Kruse CG, Sullivan K, Pruthi F, Lai M, Zhang J, Kowal DM, Carrick T, Grauer SM, Navarra RL, Graf R, Brennan J, Marquis KL, Pausch MH

Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia.

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5552-5. doi: 10.1016/j.bmcl.2009.08.050. Epub 2009 Aug 15.

PubMed ID

19720528 [ View in PubMed

]

Abstract

A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D2 receptor ligands in an attempt to identify potent D2 partial agonist/SRI molecules for treatment of schizophrenia. This approach has the potential to treat a broader range of symptoms compared to existing therapies. Selected compounds in this series demonstrate high affinity for both targets and D2 partial agonism in cell-based and in vivo assays.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Escitalopram	Sodium-dependent serotonin transporter	Ki (nM)	1	N/A	N/A	Details
Haloperidol	Dopamine D2 receptor	Ki (nM)	3	N/A	N/A	Details