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 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. On the basis of both in vitro and in vivo experiments fluvoxamine has been characterized as a potential anti-depressant drug with almost exclusively 5-hydroxytryptamine (5-HT) uptake inhibiting properties. 2. Fluvoxamine is effective in inhibiting 5-ht uptake by blood platelets and brain synaptosomes. Due to inhibition of the membrane pump the compound prevents 5-HT depletion by the tyramine-derivatives H 75/12 and H 77/77. As a result of the interference with the neuronal re-uptake mechanism for 5-HT, fluvoxamine produces a decreased 5-HT turnover in the brain. Effects of 5-hydroxytryptophan (5-HTP) are potentiated in mice and in combination with pargyline, fluvoxamine induces 5-HT-like behavioural effects. 3. In contrast to tricyclic antidepressants, noradrenaline uptake processes are either unaffected or only slightly inhibited by fluvoxamine. The noradrenaline depleting effects of tyramine derivates are not influenced by fluvoxamine. Reserpine effects, such as ptosis are affected only at very high doses of the test compound. The antagonism by fluvoxamine of the reserpine-induced lowering of the pentamethylenetetrazole convulsive threshold can be regarded as due to an effect upon 5-HT uptake. In contrast to the effects of desmethylimipramine and imipramine, no stimulatory effects are found in rats when rapidly acting reserpine-like compounds are given following a dose of fluvoxamine.
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PMID:Fluvoxamine, a specific 5-hydroxytryptamine uptake inhibitor. 30 26

The effects of viloxazine, a clinically effective antidepressant, on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake and various related pharmacological activities were determined and compared to those of the tricyclic antidepressants desimipramine, imipramine, and amitriptyline. Viloxazine inhibitied [3H]NA uptake in the mouse and rat heart, being maximally about one half as potent as imipramine with a similar onset, but shorter duration of action than imipramine. The drug did not inhibit [3H]NA uptake in rat medulla or hypothalamus in contrast to desimipramine and imipramine, but it did alter [3H]NA metabolites in a similar manner. Viloxazine, like desimipramine, was a weak blocker of mouse brain 5-HT uptake, but differed from desimipramine as it poteniated 5-HT-mediated functions in the mouse and rat, as did imipramine and amitriptyline, the latter drugs being relatively potent blockers of 5-HT uptake. Viloxazine potentiated the L-DOPA behavioural syndrome in the mouse, antagonized reserpine-induced ptosis and hypothermia in the mouse, and inhibited gastric acid secretion in the rat, but was less potent than the tricyclic antidepressants. No appreciable in vivo inhibition of monoamine oxidase (EC 1.4.3.4.) activity in the mouse was exhibited. Like imipramine, the drug potentiated the ocular effects of L-adrenaline in the rabbit. It was similar to imipramine in potency in potentiating the apomorphine-induced gnawing in the mouse. The drug antagonized oxotremorine-induced hypothermia in the mouse but differed from the tricyclic antidepressants in not exhibiting the anticholinergic effects of blocking the tremors, salivation and lacrimation. Thus, viloxazine exhibits activities related to the biogenic amines both similar to and different from the tricyclics desimipramine, imipramine, and amitriptyline. These actions appear to be of relevance with respect to the antidepressant action of this drug.
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PMID:Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities. 97 78

The central action of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride (pirlindole, PIR) in mice and rats was studied. PIR inhibited the 3H-5-hydroxytryptamine (5-HT) uptake in the rat cerebral cortex, not affecting the uptake of 3H-noradrenaline. PIR counteracted the reserpine ptosis but did not alter the apomorphine hypothermia. It enhanced the L-dopa effect on the locomotor activity and the L-5-hydroxytryptophan (L-5-HTP)-induced head twitch reaction in mice. PIR also facilitated the effect of L-dopa and L-5-HTP on the hind limb flexor reflex of the spinal rat. The clonidine sedation (but not hypothermia) was attenuated by PIR. PIR given repeatedly for 18 days increased the binding of 3H-prazosin in the brain cortex (decreasing the KD value), but did not affect the binding of 3H-dihydroalprenolol. The obtained results indicate that PIR inhibits the 5-HT uptake, displays characteristics of a monoamineoxidase inhibitor and, when given repeatedly, increases the binding to alpha 1-adrenoceptors in the cerebral cortex.
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PMID:Central action of the antidepressant drug pirlindole. 349 Aug 54

Carbamazepine (CBZ) was studied in mice and rats with regard to its antidepressant activity. CBZ did not counteract hypothermia and ptosis induced by reserpine, hypothermia evoked by apomorphine, or sedation and hypothermia induced by clonidine. CBZ shortened the immobility time in the behavioral despair test in rats (but not in mice). It attenuated hyperactivity evoked by d-amphetamine, not affecting stereotypy induced by that drug. CBZ inhibited head twitches evoked by 5-HTP, as well as the hind limb flexor reflex of the spinal rat, having no effect on its stimulation by noradrenaline and 5-hydroxytryptamine agonists. CBZ administered repeatedly did not enhance clonidine aggressiveness or d-amphetamine locomotor hyperactivity, acting differently than many antidepressant drugs. The obtained results indicate that CBZ is not similar in its action to typical and many atypical antidepressants.
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PMID:The central action of carbamazepine as a potential antidepressant drug. 404 Oct 37

1. Ouabain given by intracerebroventricular injection to mice in small doses (0.1-0.4 mug) produced a dose related depression of central nervous activity, characterized by a reduction in spontaneous locomotor activity, hypothermia, catalepsy and ptosis, lowered body posture and lack of response to external stimuli. Doses above 0.4 mug were excitatory, convulsant and lethal.2. The depressant effects could be antagonized by (+)-amphetamine, desmethylimipramine, dibutyryl cyclic 3'5'-adenosine monophosphate and caffeine.3. The MAO inhibitor nialamide produced only a small antagonism of ouabain, resulting in a greater rate of recovery from the depressant effects of ouabain.4. The depressant effects were associated with a marked elevation of whole-brain dopamine levels with little change in noradrenaline or 5-hydroxytryptamine.5. The dopamine-beta-hydroxylase inhibitor sodium diethyldithiocarbamate, administered by intracerebroventricular injection, produced effects qualitatively similar to those seen after ouabain.6. An interference with central transmitter function is postulated as a possible mode of action of intracerebroventricularly injected ouabain.
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PMID:Pharmacological properties of centrally administered ouabain and their modification by other drugs. 432 23

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. Similarly, only DCLOM was effective in the behavioral despair test in rats. DCLOM increased the 5-hydroxytryptamine (5-HT) pressor effect in pithed rats, but to a lesser extent than CLOM by several factors. Only DCLOM increased the noradrenaline (NA) pressor effect. The depletion of NA induced by 6-hydroxydopamine was depressed by DCLOM only. The 5-HT depletion induced by p-chloromethamphetamine was antagonized only by CLOM. The results obtained show that the noradrenergic mechanism is of prime importance in the action of DCLOM and of much more importance than in the action of CLOM.
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PMID:Comparison of the pharmacological actions of desmethylclomipramine and clomipramine. 621 80

Rasagiline [N-propargyl-1R(+)-aminoindan; TVP1012] is a potent irreversible monoamine oxidase (MAO) inhibitor with selectivity for type B of the enzyme, which is being developed for treatment of Parkinson's disease. In this study we examined effects of rasagiline on CNS monoamine levels, modification of behavioural response to L-tryptophan, fluoxetine and L-DOPA, and reversal of reserpine syndrome. Reserpine-induced ptosis was reversed by rasagiline at doses above 2 mg x kg(-1) i.p., which inhibit MAO-A as well as MAO-B, but not at MAO-B-selective doses. However, combination of rasagiline (10 mg x kg(-1) i.p.) with L-DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.) with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural hyperactivity syndrome which is seen following inhibition of both MAO-A and MAO-B by tranylcypromine together with the monoamine precursors. Following oral administration, levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) were unaffected in hippocampus and striatum after single doses of rasagiline up to 2 mg x kg(-1). Following chronic oral administration (21 days, one dose daily), levels of NA, 5-HT and DA in hippocampus and striatum were unaffected by rasagiline at doses up to 1 mg x kg(-1). Rasagiline does not modify CNS monoamine tissue levels or monoamine-induced behavioural syndromes at doses which selectively inhibit MAO-B but not MAO-A.
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PMID:Pharmacological properties of the anti-Parkinson drug rasagiline; modification of endogenous brain amines, reserpine reversal, serotonergic and dopaminergic behaviours. 1250 17

Methyldopa potentiated hypnosis due to hexobarbitone in mice, as did reserpine, chlorpromazine and 5-hydroxytryptamine. Methyldopa antagonized the increase by reserpine of sleep due to hexobarbitone, but enhanced the potentiation by chlorpromazine and 5-hydroxytryptamine of hypnosis due to hexobarbitone. The sedative effect of reserpine in mice and the emetic effect in pigeons were also antagonized by methyldopa. However, the effects of reserpine on convulsions due to leptazol and in causing ptosis were not antagonized by methyldopa. It is suggested that some effects of reserpine (potentiation of hexobarbitone-sleeping time, sedation and emesis) are unrelated to changes in brain amine levels and that methyldopa, with its weak reserpine-like actions, is an antagonist to reserpine.
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PMID:INFLUENCE OF METHYLDOPA ON CENTRAL EFFECTS OF RESERPINE. 1419 Apr 71

The present study aimed to investigate the antidepressant potential of genipin and its possible mechanisms. Mouse models of depression including the forced swimming test (FST) and the tail suspension test (TST) were used to evaluate the effects of genipin. A possible mechanism was explored in the test of antagonism of reserpine-induced ptosis and hypothermia in mice. The contents of monoamine neurotransmitters and their metabolites including epinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in mice hippocampi were determined by HPLC-ECD. The results showed that intra-gastric administration of genipin at 50, 100, 200mg/kg or fluoxetine at 7.5mg/kg for 7 days significantly reduced the duration of immobility in FST and TST, while it did not affect the locomotor activity in the open field test (OFT). However, the effect was not dose-dependent. When the mice were treated with genipin or fluoxetine for 7 days, both of them could antagonize reserpine-induced ptosis and hypothermia. The 5-HT and NE contents in mice hippocampi were decreased after the peritoneal injection of reserpine at 2.0mg/kg. The pre-treatment with genipin at 50, 100, 200mg/kg or fluoxetine at 7.5mg/kg for 7 days could elevate the contents of NE and 5-HT in mice hippocampi significantly. The results suggest that compared with fluoxetine, genipin exerts antidepressant-like effects significantly. A possible mechanism, at least in part, is the regulation of the 5-HT and NE levels in the hippocampus.
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PMID:Antidepressant-like effect of genipin in mice. 2056 35

Total ginsenosides have been shown to have therapeutic actions as antidepressants. We report a major active ingredient of total ginsenosides, the ginsenoside Rb3 (Rb3), which may have antidepressant-like effects. Using the forced swim test, tail suspension test, and learned helplessness procedure, we found that Rb3 had significant anti-immobility effects in mice in the forced swim and tail suspension tests and reduced the number of escape failures in the learned helplessness procedure. In a reserpine-induced syndrome model, Rb3 attenuated hypothermia, palpebral ptosis, and akinesia. In the chronic mild stress model, chronic Rb3 administration reversed the decrease in locomotor activity, novelty-suppressed feeding, and sucrose preference. Furthermore, neurochemical tests were performed to support our hypothesis that biochemical variations (i.e. brain-derived neurotrophic factor and the monoamine neurotransmitters 5-hydroxytryptamine, dopamine, and norepinephrine) are involved in Rb3's antidepressant-like effects. Finally, we found, using whole-cell patch-clamp recordings, that the action potential transmission in neurons within the somatosensory cortex was excited by Rb3 perfusion and blocked with Panax notoginseng total saponins extracted from leaves. This study provides evidence for the mechanism of action of the antidepressant-like effects of Rb3.
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PMID:Ginsenoside Rb3 exerts antidepressant-like effects in several animal models. 2194 36


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