Effects of tricyclic and tetracyclic antidepressants on the three subtypes of GABA transporter.
We examined the effects of 11 antidepressants on the activities of three-rat GABA transporters (GAT1, GAT2 and GAT3) expressed in COS-7 cells. Desipramine and maprotiline inhibited all subtypes of GABA transporter, while doxepin, mianserin, trimipramine, nortriptyline and amitriptyline inhibited certain types of GABA transporters. Amitriptyline inhibited the GAT1 and GAT3 at the reasonable dosage for clinical administration. These results suggest that the inhibition of GABA uptake might have some role in the prescribed antidepressive and sedative nature of this drug.
Nakashita
M
M
Laboratory of Molecular Pharmacology, Kobe University, Japan.
Sasaki
K
K
Sakai
N
N
Saito
N
N
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D050485:GABA Plasma Membrane Transport Proteins; D008376:Maprotiline / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects*; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; C493415:Slc6a1 protein, rat; D000639:Amitriptyline; D008376:Maprotiline; D003891:Desipramine