title: Benzothiazoles as probes for the 5HT1A receptor and the serotonin transporter (SERT): a search for new dual-acting agents as potential antidepressants.
abstract: The synthesis and evaluation of several benzothiazole-based compounds are described in an attempt to identify novel dual-acting 5HT(1A) receptor and SERT inhibitors as new antidepressants. Binding affinities at the 5HT(1A) receptor and the serotonin transporter do not appear to be congruent and other areas of the binding sites would need to be explored in order to improve binding simultaneously at both sites. Compounds 20 and 23 show moderate binding affinity at the 5HT(1A) receptor and the SERT site and thus, have the potential to be further explored as dual-acting agents. In addition, compound 20 binds with low affinity to the dopamine transporter (DAT), the norepinephrine transporter (NET) and 5HT(2C) receptor, which are desirable properties as selectivity for SERT (and not DAT or NET) is associated with an absence of cardiovascular side effects.
authors.affiliation: Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
authors.forename: Xue Y
authors.initials: XY
authors.lastname: Zhu
authors.forename: Jagan R
authors.initials: JR
authors.lastname: Etukala
authors.forename: Suresh V K
authors.initials: SV
authors.lastname: Eyunni
authors.forename: Vincent
authors.initials: V
authors.lastname: Setola
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: Seth Y
authors.initials: SY
authors.lastname: Ablordeppey
mesh_terms: D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D015195:Drug Design; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000928:Antidepressive Agents; D052160:Benzothiazoles; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A