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3-[(Aryl)(4-fluorobenzyloxy)methyl]piperidine derivatives: high-affinity ligands for the serotonin transporter.
- Source :
-
The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2007 Oct; Vol. 59 (10), pp. 1439-45. - Publication Year :
- 2007
-
Abstract
- The structural requirements for high-affinity binding at the serotonin transporter (SERT) have been investigated through the preparation of some 3-[(aryl)(4-fluorobenzyloxy)methyl]piperidine derivatives. The affinity of synthesised piperidinic compounds (1-4) at the SERT was evaluated by displacement of [3H]-paroxetine binding. Derived inhibition constant (Ki) values were in the same order of magnitude as that of fluoxetine, ranging between 2 and 400 nM. To better define the profiles of these compounds as potential antidepressants, binding affinity for 5-HT1A receptors and alpha2-adrenoceptors was also investigated by competition experiments using [3H]8-hydroxy-2-(dipropylamino)tetralin ([3H]8-OH-DPAT) and [3H]rauwolscine as radiolabelled ligands, respectively. Inhibition data indicate that compounds 1-4 possess a very weak affinity for these receptors. The high affinity of compound 1 for SERT indicates that it is worth investigating further.
- Subjects :
- Animals
Antidepressive Agents administration & dosage
Antidepressive Agents chemical synthesis
Binding, Competitive
Cerebral Cortex metabolism
Dose-Response Relationship, Drug
Fluoxetine pharmacology
In Vitro Techniques
Ligands
Piperidines administration & dosage
Piperidines chemical synthesis
Rabbits
Rats
Rats, Wistar
Receptor, Serotonin, 5-HT1A drug effects
Receptors, Adrenergic, alpha-2 metabolism
Serotonin Plasma Membrane Transport Proteins drug effects
Structure-Activity Relationship
Antidepressive Agents pharmacology
Piperidines pharmacology
Receptor, Serotonin, 5-HT1A metabolism
Serotonin Plasma Membrane Transport Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3573
- Volume :
- 59
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17910821
- Full Text :
- https://doi.org/10.1211/jpp.59.10.0016