Fluvoxamine, a new antidepressant drug, fails to show antiserotonin activity.

Fluvoxamine, (E)-5-methoxy-4'-(trifluoromethyl)valerophenone O-2(2-aminoethyl)oxime, a new antidepressant drug inhibiting serotonin (5-HT) uptake, was studied in rats and mice in order to check whether it has any central anti-5-HT activity, as do some tricyclic antidepressants, e.g. amitriptyline and doxepin.

Atypical antidepressant drugs - psychopharmacological profile and mechanism of action.

The psychopharmacological profile and mechanism of action of ten atypical novel and potential antidepressive drugs (AD) have been investigated. It has been shown that they form a pharmacologically heterogeneous group. Some of them may be considered as central 5-hydroxytryptamine (5-HT) antagonists.

Different pharmacokinetic and pharmacological effects following acute and chronic treatment with imipramine.

Two schedules of imipramine (IM) administration were compared, a single intraperitoneal dose (10 mg/kg) (I) and chronic oral dosage (10 mg/kg twice a day for 14 days) (II). During schedule I, IMI reached maximal concentration in brain twice as high as that of its metabolite, desipramine (DMI), but disappeared more rapidly. During schedule II, DMI achieved concentrations twice as high as those of IMI which were maintained in a long-lasting plateau and there were considerable differences in areas of brain concentration curves.

Effects of chronic treatment with antidepressants on aggressiveness induced by clonidine in mice.

It has previously been found that a number of typical and atypical antidepressants, given chronically, intensify clonidine-induced aggressiveness in mice. Further experiments now show that chronic, but not acute, administration of nisoxetine, a selective inhibitor of noradrenaline uptake, potentiates clonidine-induced aggressiveness. Citalopram and fluvoxamine, two selective inhibitors of serotonin uptake, have no such action.

Comparison of the pharmacological actions of desmethylclomipramine and clomipramine.

This research compares the effects, in mice and rats, of desmethylclomipramine (DCLOM) and clomipramine (CLOM). DCLOM antagonized the hypothermia induced in mice by reserpine or apomorphine to a much greater extent than CLOM. Reserpine ptosis in mice was depressed by DCLOM only.

[Effect of memantine on central neurotransmitter systems. Review of the results].

In the present review the effects of 1,3-dimethyl-5-amino-adamantane (DMAA, D-145, Memantine, Memantine) on various neurotransmitter systems were presented. The most marked effect of DMAA seems to be the stimulation of dopaminergic neurons as reflected by the respective behavioural changes and biochemical effects. The stimulatory action on noradrenaline and serotonin neurons (at least partially indirectly through the activation of dopamine system) as well as on GABA neurons is apparent.

Influence of proadifen, an inhibitor of the metabolism of drugs, on the action of imipramine and desipramine in rats.

The influence of proadifen (SKF-525-A), an agent inhibiting the metabolism of drugs, on the antidepressant action of imipramine (IMI) and desipramine (DMI) in rats was investigated. Proadifen antagonized the action of IMI when investigated in reserpine hypothermia and ptosis and in the behavioral despair test. The action of DMI in the same tests was not changed by proadifen.

Chronic treatment with some atypical antidepressants increases the brain level of 3-methoxy-4-hydroxyphenylglycol (MHPG) in rats.

We examined the effects of some atypical antidepressants with central antiserotonergic activity (mianserin, trazodone, danitracen, pizotifen), and 5-HT receptor blocking agents (cyproheptadine and metergoline), on whole rat brain levels of the main noradrenaline (NA) metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG). In acute experiments, when drugs were injected in a single dose 1, 2, 4, 24 or 48 h before decapitation, only mianserin elevated the MHPG level. In chronic experiments (drugs given b.

Chronic treatment with antidepressants: protentiation of clonidine-induced aggression in mice via noradrenergic mechanism.

The chronic (10 mg/kg i.p. twice daily, 10 days)-and not the acute-administration of amitriptyline, maprotiline or zimelidine enhances aggressiveness induced by clonidine in mice.

Pharmacological properties of Craviten (M-71).

The preparation Craviten (M-71) produced by POLFA Pharmaceutical Works in Cracow (2S, 2'S) N, N'-dimethyl-N, N'-bis-[1-(3',4',5'-trimethoxybenzoyloxy)-butyl]-2-ethylenediamine dihydrochloride) prevents and abolishes heart rhythm disturbance induced in the rat with BaCl2, CaCl2, adrenaline or aconitine. The doses effectively preventing arrhythmia development were in the range from 0.035 to 0.

Central action of Craviten (M-71).

Craviten (M-71) or 2S, 2'S) N, N'-dimethyl-N, N'-bis [1-(3', 4', 5' -trimethoxy-benzoyloxy)-butyl-2]-ethylenediamine dihydrochloride an agent with a strong antiarrhythmic action has practically no effect on the central nervous system of rats and mice. It exerts no effect on the spontaneous motor activity, on amphetamine-stimulated hyperactivity, on rota-red performance, it has no analgesic and anticonvulsant action and does not change the hexobarbital sleeping time. No effects of Craviten were observed on the body temperature in rats and mice.

Effects of chronic administration of antidepressant drugs on aggressive behavior induced by clonidine in mice.

The effects of antidepressant drugs on clonidine-induced aggressive behavior were determined in mice. Imipramine, mianserin and iprindole used in a single dose attenuated clonidine-induced aggression. Their chronic administration enhanced it.

Central serotoninmimetic action of phenylpiperazines.

Studies of 1-(m-chlorophenyl)-piperazine (m-CPP), 1-(p-chlorophenyl)-piperazine (p-CPP) and 1-phenylpiperazine (PP) were carried out on rats, mice and rabbits in order to assess their stimulatory effect on the central serotonin system. It was found out that m-CPP and p-CPP evoked a characteristic syndrome in the mouse behavior. All the phenylpiperazine derivatives stimulated the flexor reflex in the spinal rat and evoked hyperthermia in rats at a high ambient temperature (28 degrees C) and in rabbits.

Central action of mepiprazole.

Mepiprazole, a phenylpiperazine derivative, strongly antagonizes the behavioral syndromes evolved by 5-hydroxytrypotophan. The drug did not affect the serotonin neurons in the preparation of flexor reflex of the hind paw of the spinal rat: in higher doses it depressed the reflex showing noradrenolytic properties. Mepiprazole antagonized the fenfluramine-induced hyperthermia, depressed spontaneous locomotor activity, produce hypothermia and was inactive in the despair test.

Zimelidine and clomipramine: different influence on fenfluramine but not p-chloroamphetamine-induced pharmacological effects.

The influence of zimelidine and clomipramine on two p-chloroamphetamine (PCA)- or fenfluramine-induced pharmacological effects, regarded as resulting from the serotoninergic stimulation, was studied. In the flexor reflex test in the spinal rat zimelidine prevented potentiation induced by PCA but not that induced by fenfluramine. Clomipramine antagonized both the PCA- and fenfluramine-induced effects.

Chronic treatment with antidepressant drugs: potentiation of apomorphine-induced aggressive behaviour in rats.

Chronic (14 days) but not acute treatment with antidepressants (amitriptyline, imipramine, desipramine, clomipramine, mianserin, danitracen, iprindole) potentiated the aggressive behaviour induced by apomorphine (APO) in rats. The APO stereotypy was not changed. A similar potentiation was caused by chronic treatment with phentolamine or thioridazine but not with spiperone or deazepam.

Central antiserotonin action of amitriptyline.

Amitriptyline (AMI) was studied in rats snd mice in order to find out whether it had a central antiserotonin activity, previously demonstrated for doxepin - a compound chemically related to AMI. It was observed that AMI at low doses antagonized the head twitch response to L-5-hydroxytryptophan or 5-methoxytryptamine, as well as tryptamine-induced convulsions. In the hind limb flexor reflex preparation of the spinal rat AMI acted as a serotonin antagonist: when administered alone, it did not change the flexor reflex but prevented its stimulation induced by serotoninmimetics (LSD, quipazine, fenfluramine) not affecting that one evoked by noradrenalinemimetics (clinidine).

On the central antiserotonin action of trazodone.

Trazodone, an antidepressant drug with an unknown mechanism of action, has been examined in order to demonstrate its central antiserotonin action. Trazodone antagonizes the head twitch response induced by 5-hydroxytryptophan in rats and mice, or by-5-methoxytryptamine in rats (the ED50 values are 9.3, 5.

Trazodone, a central serotonin antagonist and agonist.

We examined the effect of trazodone (TR), a non-tricyclic antidepressant drug with an unknown mechanism of action, as well as its supposed metabolites beta-(3-oxo-s-triazolo-[4, 3 a]-pyridin-2-yl-propionic acid (OTPA) and 1-(m-chlorophenyl)-piperazine (CPP) on the serotonin (5-HT) -system in a model of the hind limb flexor reflex of the spinal rat. When given alone at low doses (1 mg/kg) TR does not change the flexor reflex but counteracts its serotonergic stimulation induced by LSD, quipazine or fenfluramine. At higher doses (6--8 mg/kg), after a period of latency, it enhances the reflex; this effect is antagonized by the 5-HT receptor blockers (cyproheptadine, WA-335 and metergoline) but not by imipramine.

The effect of repeated administration of antidepressant drugs on the responsiveness of rats to catecholamine agonists.

The antidepressant drugs, imipramine (10 mg/kg s.c.), amitriptyline (10 mg/kg s.