Biological and Pharmacokinetic Evidence for Generic Equivalence of Three Imipramine Preparations: Comparison with a New Imipramine Analogue

The biological availability of three imipramine preparations and an imipramine analogue, Leo 640, has been studied using a recently developed biological procedure. The isolated rat iris, was used to elucidate the inhibitory power of these drugs on noradrenaline uptake into adrenergic nerve terminals. Irides incubated in patients’ plasma before and during drug treatment were compared in two series of cross‐over studies on hospitalized patients. It was found that the drugs compared seemed to be identical with regard to their effect on noradrenaline neurons. It has been hypothesized that the antidepressive effect of this type of tricyclic drugs is brought about by their inhibition of reuptake of monoamines released into central synapses. This method provides a new way for comparing these drugs and their active metabolites at the presumed site of action.