Effects of lithium on alterations of pharmacokinetics of imipramine and on the related changes of monoamines in rat brain.
Rats were given chronically i.p. imipramine (20 mg/kg), LiCl (1 mg/kg) or both drugs to examine the effects of lithium (Li) on the alterations of imipramine pharmacokinetics in the whole brain and on the imipramine-related changes of norepinephrine (NE) and serotonin (5-HT) levels in the brain. When rats were given Li for 3 days, followed by a single injection of imipramine, the concentrations of desipramine in the brain and serum were higher than those in the vehicle-treated rat, although the imipramine concentrations in both tissues did not differ in Li- and in vehicle-treated rats. In rats receiving both drugs for 10 days, the steady state levels of imipramine and desipramine in the brain were the same as those in the vehicle-treated rats but the steady state level of desipramine was reached earlier with Li treatments presumably because of the enhanced demethylation of imipramine. Consequently, the desipramine-dependent alterations of NE and 3-methoxy-4-hydroxyphenylglycol levels in the brain appeared to be induced earlier and more markedly when Li was given simultaneously. As the 5-hydroxyindole acetic acid (5-HIAA) levels were elevated in the brains of Li-treated rats and reduced in brains of imipramine-treated rats as compared with the level in vehicle-treated rats, the 5-HIAA level in rats receiving both drugs was equivalent to that in vehicle-treated rats.
Yoshida
T
T
Department of Neuropsychiatry, Aichi Medical College, Japan.
Suzuki
S
S
Sugita
S
S
Kobayashi
A
A
Nakazawa
K
K
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D007099:Imipramine / Q000493:pharmacokinetics*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D015306:Biogenic Monoamines; D002395:Catecholamines; D012701:Serotonin; D008094:Lithium; D007099:Imipramine