Metabolism of 5-hydroxytryptamine and levels of tricyclic antidepressant drugs in rat brain after acute and chronic treatment.
Because tricyclic antidepressants (TAD) are usually given chronically to patients, both their acute and their chronic effects on 5-hydroxytryptamine (5-HT) metabolism were studied. The probenecid method was used and, in addition to 5-hydroxy-indoleacetic acid (5-HIAA), some other indole compounds in brain were measured. Simultaneously, TAD levels in brain and plasma were determined. Dimethylated as well as monomethylated TADs were administered, both at 10 and 25 mg/kg i.p. Treatment with either 10 mg/kg during 14 days or 25 mg/kg given acutely resulted in a similar brain level of TAD, so any differences found could be attributed to differences in administration schedule. Drug levels in brain and plasma differed considerably after chronic and acute treatments but no major differences in the effect on 5-HIAA level in the brain were found, although accumulation of 5-HIAA following probenecid treatment was mostly lowered after treatment with dimethylated TAD. The TAD level in rat brain was not decisive for the effect on central 5-HT turnover. The monomethylated TAD affected the 5-HT turnover very little, not only acutely but also chronically.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004334:Drug Administration Schedule; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D011339:Probenecid / Q000494:pharmacology; D011530:Protriptyline / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D012701:Serotonin; D011530:Protriptyline; D002997:Clomipramine; D007099:Imipramine; D011339:Probenecid; D003891:Desipramine