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It is known that some derivatives of the benzodiazepine group act not only as antipsychotic drugs but also have inhibitory effects on the growth of protozoa. The influence of imipramine and its derivatives clomipramine and desipramine on the multiplication of Crithidia luciliae, Leishmania mexicana amazonensis, Trypanosoma cruzi and Trichomonas vaginalis was investigated using in vitro cultivation of the parasites and compared with the effects of chlorpromazine and metronidazole. All trypanosomatides used were inhibited by imipramine and its derivatives with clomipramine having the strongest influence on the growth of parasites (ID50 12.5-35 micrograms/ml). The Trichomonas vaginalis strain used was susceptible to metronidazole but it was nearly resistant to the tricyclic compounds tested (ID50 greater than 100 micrograms/ml).

In metabolic tests in narcotized rats it could be demonstrated that isoprenaline under continuous intramuscular infusion is, calorigenically, about three times more effective than noradrenalin. By blocking the uptake of sympathomimetics into peripheral adrenergic neurones by means of desipramine the calorigenic effect of noradrenalin is increased thirteenfold while under isoprenaline it decreases slightly.

The influence of substances modulating the activity of central monaminergic systems on the anticonvulsant effect of propranolol was investigated with the maximal electroshock test in mice. The results demonstrated that especial the noradrenergic system plays an important role in modulating the efficacy of propranolol. Pharmacological stimulation of the noradrenergic system (e. g. with desipramine, pargyline, yohimbine) resulted in an enhanced anticonvulsant effect of propranolol. Compounds that suppress the noradrenergic transmission reduced this action. On the other hand manipulations of serotonergic (with 5,7-DHT, 5-HTP, PCPA) or dopaminergic (with 6-OHDA + desipramine, apomorphine) mechanisms seems to be without marked influence on the protective effect of propranolol in maximal electroshock.

In a series of 74 experiments in a double blind study, 25 healthy test persons were medicated with a single dose of Clomipramin, Desipramin, Imipramin, Diazepam, Carbamazepin, Haloperidol, and a placebo. At the end of one hour, and again at the end of three hours, an EEG was made whose frequency analysis revealed significant changes in about half the test persons. The antidepressives induced an increase in the theta waves, the slow alpha waves, and the slow beta waves, and a decrease in the fast alpha waves. The factors influencing the EEG are discussed.

In tests on narcotized rats dopamine and dobutamine show significant calorigenic actions By subcutaneous application dobutamine is nearly as effective as noradrenaline while dopamine acts approximately five times less. Pretreatment with desipramine increases the calorigenic action of noradrenaline and accelerates its onset and its dying down simultaneously. Such a pretreatment exerts no influence whatever on the calorigenic action of dobutamine, which begins and dies down remarkably fast. Calorigenic action of dopamine is lessened by desipramine pretreatment, unambiguously. If sympathomimetics are not taken up into the neurons or their uptake is blocked by substances like desipramine, their access to the receptors is facilitated and their biotransformation possibly favoured.

Chronic treatment of rats with desipramine leads to an increase of hippocampal neurons with low spontaneous activity. After an isolation rearing period of three months an increased spontaneous activity is seen in the hippocampus of rats. Furthermore the hippocampal spontaneous activity is related to age. Opposite alterations of spontaneous activity in desipramine treated and socially isolated rats, respectively, as well as their relations to noradrenergic transmission processes are discussed. The isolation syndrome as a model to test substances with antidepressive properties is also reviewed.

Tricyclic antidepressives (TA) exert differential effects on the circulatory system, though all of them have one principle in common: inhibition of back resorption of noradrenaline in the adrenergic synapses. Of more importance, however, seems to be the dose rather than the type of substance used. Smaller doses were found to potentiate the pressoric effects of noradrenaline, while higher doses frequently had an inhibitory action. In rats pretreated with 6-OH-dopamine, only an inhibitory action has been established. It is concluded that the TA must have a postsynaptic influence that becomes effective either through the membrane receptors and/or other factors within the cell.

The influence of Desmethylimipramin (PertofranR) on the regional uptake of 3H-leucine in different areas of rat brains has been investigated with autoradiographic methods. Male rats were injected 10 m/kg Desmethylimipramin (DMI, PertofranR) i.m. and 1 hr later 8,33 mCi 3H-leucine i.p.. 1 and 7 hrs after application 3H-leucine the animals were sacrificed. Concentrations of silvergrains of 3H-leucine activity were countered under surface illumination in varions brain areas by means of strippingfilmautoradiograms. DMI markedly depressed the concentrations of 3H-leucine-activity in all layers of the parietal cortex after 8 hrs and the depression was greater with the increase of nerv- and gliacellvolumendensity of the layers. Within 2 hrs such an influence of DMI on 3H-leucine uptake could not be found. There was a smaller decrease of 3H-leucine incorporation after DMI applications in some layers of ammon's horn, dentate gyrus and cerebellum. Some further effects of DMI and IP (Imipramine) on components concerned with protein metabolism are discussed.

Long-term treatment of rats with the antidepressive desipramine increase in the hippocampus the number of neurons with low spontaneous discharges and affects the animals' response to microiontophoretically applied noradrenalin. Additional acute administration of desipramine causes, after long-term treatment with the antidepressive, a stronger increase in noradrenalin induced inhibition of the firing rates as compared with controls.

The effects of some typical clinically tested psychotropic drugs were studied in acute experiments on awake rats. Potentials in somatosensory cortex were evoked by peripheral stimulation. Haloperidol, diazepam, medazepam, desipramin and a new substance, the MPP-sulton, caused significant modification in latency and amplitude of some components of the potentials. Between the effects of psychotropic drugs exist differences which, in turn, were clearly distinguishable from the modification of these evoked responses by unspecific narcotic effects of hexobarbital.

DMI leads to stimulation of GH in healthy male subjects 60--120 min after i.m. injection and 150--210 min after oral application. During a 20-day administration of 2 x 75 mg DMI per day a repeated stimulation of GH was provable on days 0, 10 and 20 in two male patients, whereas no stimulation of GH occurred in two female patients who underwent the same treatment. The GH basic secretion did not increase in any of the four after patients 10 and 20 days, respectively. Neither prolactin (PRL) nor thyreotrophin (TSH) serum concentrations are influenced by DMI. The increase in PRL and TSH, which is induced by the thyrotrophin releasing hormone (TRH), is provable after acute as well as after chronic administration of DMI.