Concentrations of imipramine (IMI) and desipramine (DMI) in the rat brain after administration of IMI in aqueous solution by stomach gauge twice daily, in oil solution parenterally at 48 h intervals, and with drinking water were assayed. IMI administration with the drinking water for 21 days produced a pattern of the brain concentrations of IMI and DMI similar to that observed in rats receiving IMI by stomach tube for two weeks, at 12 h intervals. When IMI was given to rats ip in an oil solution at 48 h intervals for 10 days, the brain levels of both IMI and DMI were very high and rather stable during 48 h after administration of the last dose of IMI. However, the relation between brain concentration of IMI and DMI differed markedly from that found in rats receiving IMI with the drinking water. It seems that administration of IMI with drinking water may be recommended as a reliable and convenient dosage schedule in experiments which need prolonged treatment with IMI.

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