The effect of antidepressant drugs on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist.

It was found earlier that imipramine, amitriptyline and citalopram enhanced the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist, in rats. Now, three other antidepressants: (+)-oxaprotiline, an inhibitor of the uptake of noradrenaline, (-)-oxaprotiline, an enantiomer devoid of any effect on the uptake of noradrenaline and fluoxetine, an inhibitor of the uptake of 5-hydroxytryptamine, have been examined in male Wistar rats. All those antidepressants, given in a single dose, increased the MK-801-induced locomotor hyperactivity.

The effect of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in the forced swimming test.

The present study examined the effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in the forced swimming test in rats and mice. Administered in a single dose or three times both examined compounds reduced the immobility time in rats. Active doses used in that test either did not change the locomotor activity or decreased it.

Effects of MK-801 and antidepressant drugs in the forced swimming test in rats.

The effects of MK-801, a non-competitive NMDA receptor antagonist, and of antidepressant drugs were studied in the forced swimming test in rats. MK-801 reduced immobility time. Combined treatment with MK-801 + imipramine induced a stronger effect in Porsolt's test than administration of either drug alone.

The effect of (+)- and (-)-oxaprotiline administered repeatedly on the dopamine system.

The behavioural and biochemical effects of repeated (14 and 28 days) treatment with (+)-oxaprotiline (a noradrenaline uptake inhibitor) and (-)-oxaprotiline (levoprotiline, without influence on noradrenaline uptake; the clinically active antidepressant) were studied in rats. Both those enantiomers given repeatedly increased the locomotor and exploratory activity and reduced the immobility time in Porsolt's test. The D-amphetamine-induced locomotor hyperactivity, as well as the stereotypies induced by D-amphetamine and apomorphine, were increased by the oxaprotilines.

Some central effects of opipramol given repeatedly.

Some central effects of opipramol administered repeatedly (twice daily, 14 days) were studied in rats and mice. Repeated or acute treatment with opipramol did not change the locomotor activity of rats. Given repeatedly, but not in a single dose, opipramol increased the (+)-amphetamine-induced hyperactivity.

Some central pharmacological effects of (+)- and (-)-oxaprotiline.

The central action of oxaprotiline (OXA) enantiomers, administered in a single dose, was studied in rats and mice. (+)-OXA and (-)-OXA attenuated reserpine- and apomorphine-induced hypothermia [(+)-OXA in a more potent manner] in mice and reduced the immobility time in the behavioural despair test in rats. Both OXA enantiomers inhibited locomotor activity in mice and rats, and enhanced and prolonged amphetamine- and apomorphine-induced stereotypy in rats.

Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a potential therapeutic activity in Parkinson's disease.

Behavioural and some neurochemical effects of Ro 40-7592 (3,4-dihydroxy-4'-methyl-5-nitrobenzophenone), a new COMT inhibitor, were studied in rats and mice. Ro 40-7592 increased the effect of L-DOPA (plus benserazide) on locomotor activity, reserpine-induced hypothermia, and catalepsy induced by pimozide, haloperidol and fluphenazine. Locomotor hyperactivity induced by amphetamine or nomifensine, as well as stereotypy induced by amphetamine (but not apomorphine), were also increased by Ro 40-7592.

Antidepressant activities of WEB 1881, a new nootropic agent.

The central action, particularly potential antidepressant activity of WEB 1881, a new nootropic drug related to piracetam, was investigated in rats and mice. WEB 1881 antagonizes the reserpine- and apomorphine-induced hypothermia, potentiates the behavioral effect of DOPA and dihydroxyphenylserine, as well as the TRH-induced hyperthermia. Piracetam was only effective in the reserpine and DOPA tests.

The effect of repeated administration of imipramine, citalopram and mianserin on responsiveness of central serotonergic, alpha 2-adrenergic and cholinergic system in mice.

The effect of antidepressant drugs: imipramine, citalopram and mianserin given either in a single dose or twice a day for 14 days in a dose of 10 mg/kg was investigated in mice in tests for the responsiveness of central serotonergic (L-5 hydroxytryptophan-induced head twitches), alpha 2-adrenergic (donidine hypoactivity) and cholinergic (oxotremorine syndrome) systems. The effect of L-5 hydroxytryptophan was inhibited by repeated administration of citalopram and mianserin but unchanged by administration of imipramine. After a single administration only mianserin inhibited the L-5 hydroxytryptophan effect.

Antidepressants given repeatedly increase the behavioural effect of dopamine D-2 agonist.

The effects of single or repeated doses of antidepressant drugs (imipramine, amitriptyline, citalopram, mianserin) on rat locomotor hyperactivity induced by quinpirole, a dopamine D-2 receptor agonist, was investigated. Single doses of antidepressants do not change the effect of quinpirole, but enhance it when they are administered repeatedly. This enhancement is inhibited by (+/-)-sulpiride, a dopamine D-2 receptor antagonist.

Some central effects of tiflucarbine, a new potential antidepressant drug.

Tiflucarbine (TVX P 4495), a new putative antidepressant drug (AD) with a chemical novel among AD's [9-ethyl-4-fluoro-1-methyl-7,8,9,10-tetrahydrothieno (3,2-e)-pyrido(4,3-b)indole lactate], a potent inhibitor of the 5-hydroxytryptamine (5-HT) uptake, was studied in rats and mice, mostly with regard to its possible effect on the noradrenaline (NA) uptake and 5-HT postsynaptic receptors. Tiflucarbine exerted no effect on the reserpine hypothermia, attenuated the apomorphine hypothermia and enhanced the TRH-induced hyperthermia. It did not prevent tryptamine convulsions or the fenfluramine-induced hyperthermia, and inhibited the L-5-hydroxytryptophan-induced head twitches (at a high dose only).

Pharmacological properties of EXP 561, a potential antidepressant drug.

The compound EXP 561 (1-amino-4-phenylbicyclo-[2,2,2]-octane), an inhibitor of the noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) uptake, a potential antidepressant agent, was studied in tests for evaluation of antidepressant drugs (AD). In most experiments (the apomorphine and reserpine hypothermia, the behavioural despair test, the blood pressure increases induced by NA and 5-HT) EXP 561 revealed similar activities as tricyclic AD. EXP 561 evoked stimulation of the hind limb flexor reflex in spinal rats, blocked by prazosin, metergoline and clomipramine.

Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine.

The effect of repeated treatment (twice a day for 14 days) with antidepressant drugs (AD): imipramine, amitriptyline, zimelidine, citalopram and mianserin on the behavioural response to apomorphine in rats (open field test) was investigated. AD studied, given alone in a single dose or repeatedly, do not change the rats behaviour. A repeated but not single-dose treatment with AD facilitates the behaviour stimulation induced by apomorphine.

Reserpine-induced locomotor stimulation in mice chronically treated with typical and atypical antidepressants.

Previous studies have shown that chronic treatment with antidepressants (AD) leads to an increased responsiveness of NA systems to noradrenaline (NA) or its agonist. In the present paper the influence is described of a prolonged treatment with AD of different pharmacological profiles on the effect of reserpine in the first phase of its action (amine release). It has been found that in mice treated chronically (14 days, twice a day, i.

The effect of selective inhibitors of noradrenaline and serotonin uptake on reserpine- and apomorphine induced hypothermia in mice.

The antidepressant action of combined treatment with selective inhibitors of noradrenaline (NA) and serotonin (5HT) uptake was investigated using the reserpine and apomorphine hypothermia tests. Desipramine and maprotiline, NA uptake inhibitors, but not fluoxetine and citalopram, selective 5HT uptake inhibitors, antagonized the hypothermias. A combination of NA and 5HT uptake inhibitors antagonized reserpine hypothermia less effectively than the inhibitor of NA uptake alone.

The effect of proadifen, a drug metabolism inhibitor, on action of imipramine and desipramine in mice.

Proadifen (SKF 524 A) inhibited the following effects of imipramine (IMI), without affecting those of desipramine (DMI) in mice: antagonism towards reserpine-induced hypothermia, ptosis and sedation, antagonism to apomorphine hypothermia and insignificant shortening of the immobility time in the behavioral despair test. Cerebral levels of DMI were very low after administration of IMI; pretreatment with proadifen did not affect the already low levels of DMI but significantly elevated these of IMI. This may indicate that some other than DMI metabolites (e.

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.

The effect of the antihistaminic drugs on the central action of 5-hydroxytryptophan in mice.

Antihistaminic drugs of various chemical structure (chlorcyclizine, chloropyramine, chlorpheniramine, clemastine, diphenhydramine, mepyramine, promethazine, thenalidine) were tested on their action on the central serotonin system in mice. The test used was the antagonism to behavioral syndrome produced by D, L-5-hydroxytryptophan (5-HTP). Clemastine, promethazine and thenalidine inhibited 5-HTP-induced syndrome in doses of much lower than those inhibiting locomotor activity.

Effects of antihistaminic drugs in tests for antidepressant action.

Antihistaminics of various chemical structures: chlorcyclizine, chloropyramine, chlorpheniramine, clemastine, diphenhydramine, mepyramine, promethazine, and thenalidine were investigated for the action in tests for antidepressant drugs. The antihistaminics did not affect significantly the spontaneous locomotor activity of rats. Most of them (chloropyramine, chlorpheniramine, diphenhydramine, promethazine and thenalidine) increased amphetamine hypermotility but chlorcyclizine significantly inhibited, and clemastine and mepyramine did not affect it.

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.

Central action of ketotifen.

Ketotifen (4-/1-methyl-4-piperidylidene/-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one hydrogen fumarate) inhibited spontaneous locomotor activity and amphetamine hypermotility in mice and rats, as well as L-DOPA-induced motor stimulation in mice. It produced in mice a slight hypothermia and did not prevent reserpine-induced hypothermia; thus, it does not posses properties or tricyclic antidepressants. Ketotifen showed some features of serotoninolytic: it inhibited the head twitch response to 5-hydroxytryptophan in mice, depressed tryptamine-induced clonic convulsions in rats, antagonized fenfluramine-induced hyperthermia in rats at high ambient temperature and showed weak antiserotonin action in the flexor reflex preparation.

Central action of pirenzepine.

Pirenzepine, (5,11-dihydro-11-[(4-methylpiperazin-1-yl)-acetyl]-6H-pyrido-[2,3] [1,4]-benzodiazepin-6-one dihydrochloride), tested on rats and mice, did not demonstrate any conspicuous behavioral action: it did not counteract reserpine hypothermia in mice, the L-DOPA hypermotility of mice, and (with the exception of very large doses) the amphetamine hypermotility in mice and rats. The drug neither prolonged the time of immobility of rats in the behavioral despair test, nor affected the central serotonin system in rats in tests for 5-hydroxytryptophan-induced head twitches, tryptamine-induced convulsions and fenfluramine-induced hyperthermia at high ambient temperature. Pirenzepine did not affect either the hind limb flexor reflex in the spinal rat, nor the action of serotoninomimetics of it.

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.

The central antiserotonergic action of mianserin.

The central antiserotonergic action of mianserin (MS) was tested in mice, rats, and rabbits. MS, like cyproheptadine, to which it was compared, inhibits the head-twitch response to 5-hydroxytryptophan in mice and rats without affecting the pinna reflex. MS does not change the flexor reflex of the hind limb of the spinal rat; it antagonizes its stimulation induced by fenfluramine, LSD, and quipazine, but not that induced by clonidine.