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

The pharmacological profile of a new bicyclic substance, Lu 10-171 (1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalancarbonitril), is described and compared with that of existing tricyclic thymoleptics. In mice and rats the compound exhibited marked 5-HT potentiating properties both in vivo and in vitro, being 5-10 times as active as chlorimipramine. The tests included 5-HT-, 5-HTP- and tryptophan-potentiation. In monoamine oxidase inhibitor treated dogs and rabbits the compound caused a marked hyperthermia. In rabbits this effect was completely blocked by pretreatment with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine. Hyperthermia induced by the central catecholamine displacing substance H 77/77 in rats was not affected by Lu 10-171, whereas the substance abolished the temperature rise induced by H 75/12. Reserpine- and tetrabenazine-induced ptosis and tetrabenazine-induced immobility in mice were antagonized by relatively low doses of existing tricyclic thymoleptics, whereas Lu 10-171 was very weak in this respect. Very weak in vitro anticholinergic and antihistaminergic properties were also registered for Lu 10-171. It is concluded that Lu 10-171 is a very potent and highly specific potentiator of 5-HT both in vivo and in vitro probably due to inhibition of 5-HT uptake. Thus this compound might be a useful agent in studying the role of 5-HT neurone systems in the control of mood. The substance does not possess the NA potentiating and anticholinergic and antihistaminergic properties characteristic of the tricyclic antidepressants.
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PMID:Pharmacology of a new phthalane (Lu 10-171), with specific 5-HT uptake inhibiting properties. 1 88

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

Fengabine (SL 79.229) is a novel benzylidene derivative with clinically proven antidepressant action. Fengabine is active in behavioral models for antidepressant drug action, reversing the passive avoidance deficit in olfactory bulbectomized rats, antagonizing the escape deficit in the learned helplessness model and decreasing paradoxical sleep in the rat. In contrast to tricyclic antidepressants, fengabine antagonizes 5-hydroxytryptophan-induced head twitches and only weakly reverses reserpine-induced ptosis. Fengabine inhibits neither monoamine uptake nor monoamine oxidase. A GABAergic mechanism of fengabine is indicated as bicuculline reverses its action in the olfactory bulbectomy and learned helplessness models. The wide-spectrum anticonvulsant action of fengabine is consistent with a GABA-mimetic action and is in contrast to the proconvulsant effect of most classical antidepressants.
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PMID:Fengabine, a novel antidepressant GABAergic agent. I. Activity in models for antidepressant drugs and psychopharmacological profile. 303 3

2-Amino-2-oxazolines are heterocyclic compounds with interesting pharmacological properties. Several derivatives of this chemical series were studied in psychopharmacological tests. One derivative 4,5-dihydro-5-[methyl(4-phenyl-1-piperazinyl)]-2-oxazolamine (COR 32-24), had an antidepressant profile. Its structure can be compared to trazodone in its phenylpiperazine group and to toloxatone in its oxazoline group. This molecule antagonized reserpine-induced hypothermia and ptosis, oxotremorine-induced hypothermia and high-dose apomorphine-induced hypothermia. It also potentiated yohimbine-induced sublethality and decreased the immobility of forced swimming. It had no monoamine oxidase inhibitory activity. These results suggest a profile close to that of viloxazine and to that of a classic antidepressant.
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PMID:A 2-amino-2-oxazoline derivative as an antidepressant in mice. 326 82

A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones was prepared and evaluated for potential antidepressant activity. Members of this series were generally prepared by the alkaline ring closures of the corresponding 1-aroylthiosemicarbazides. Several members of this series were potent antagonists of both RO 4-1284-induced hypothermia and reserpine-induced ptosis in mice. In general the more active members of this series were substituted by haloaryl groups at the 5-position of the triazole nucleus and by methyl groups at the 2- and 4-positions. Exchange of the thiocarbonyl group at the 3-position for a carbonyl group resulted in the complete loss of activity. Biochemical evaluation of the more active members of this series indicated that the aforementioned activities were not a consequence of either norepinephrine (NE) uptake or monoamine oxidase inhibition. In an attempt to determine a mechanism of action, one member of this series, compound 22, was selected for further evaluation in an electrophysiological model where it was found to reduce norepinephrine function in the cerebellum as measured by the NE augmentation of GABA inhibition of Purkinje neurons.
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PMID:2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents. 337 95

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.
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PMID:[Pharmacological properties of MO-8282, a novel antidepressant]. 379 61

The new substance (+/-)8-chloro-1,2,3,4,10,10a-hexahydro-2-methyl-4a,10-(iminoethano )-4aH -[1]benzopyrano[3,2-c]pyridin-12-one (4a alpha,10 alpha,10a alpha) (lortalamine, LM 1404) is compared with imipramine in a series of pharmacological and biological tests. Lortalamine antagonises in a dose-related manner reserpine-induced ptosis and hypothermia, and is far more potent than imipramine in this regard. The compound potentiates yohimbine toxicity in mice and, in the anesthetized dog, diminishes the tyramine pressure response while increasing the response to norepinephrine. These results would indicate the capacity for lortalamine to act as a norepinephrine uptake inhibitor, and indeed, lortalamine is more potent than imipramine in inhibiting norepinephrine uptake by rat brain cortex slices. Lortalamine does not inhibit serotonin uptake by rat midbrain slices and neither interferes with 5-hydroxytryptophan and p-chloroamphetamine in mice. The interference with the dopaminergic system seems to be slight or even negligible, since the compound does not interfere with apomorphine or amphetamine in mice; moreover, dopaminergic uptake by rat striatum synaptosomes is inhibited only at very high concentrations. Lortalamine does not modify norepinephrine release, MAO activity nor behaviour of mice. Contrary to tricyclic antidepressants, lortalamine is devoid of anticholinergic and antihistaminic properties. The vegetative and cardiovascular effects as studied in the anesthetized dog are either absent or very slight. In particular, heart conduction is far less impaired in comparison to imipramine, which correlates with the absence of local anesthetic properties of the product.
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PMID:Pharmacology of lortalamine, a new potent non-tricyclic antidepressant. 409 69

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

5-(4-Dimethylaminobenzyl)imidazolidine-2,4-dione was prepared by catalytic hydrogenation of the corresponding benzylidene compound. Antidepressant testing in mice indicated that its ED50 values for antagonism of tetrabenazine-induced ptosis and potentiation of levodopa-induced behavioral changes were 42 and 17 mg/kg po, respectively. In vitro neurochemical studies demonstrated that this compound did not inhibit the uptake of selected biogenic amines into crude synaptosomes of mouse whole brain, and it did not have significant monoamine oxidase inhibitory activity in vivo and vitro. Thus, this compound possesses potential antidepressant activity with a mechanism different from that of the tricyclic antidepressants and monoamine oxidase inhibitors.
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PMID:Synthesis and antidepressant activity of 5-(4-dimethylaminobenzyl)imidazolidine-2,4-dione. 610 54

A series of 5-phenyl-2-furamidines has been synthesized and evaluated for antidepressant activities. Substitution in the phenyl ring with a nitro (4) or an amino (12) group in the ortho-position resulted in an increase in antidepressant activity. Both 4 and 12 antagonized tetrabenazine-induced ptosis in rodents and inhibited norepinephrine (noradrenaline) uptake into crude synaptosomes of whole mouse brain at doses or concentrations comparable to those of the tricyclic antidepressants. However, these compounds did not possess the anticholinergic and antihistaminic activities common to tricyclic antidepressants. In addition, they lacked monoamine oxidase inhibitory activity. The 5-phenyl-2-furamidines represent a new chemical class of antidepressants and may be useful for depressive patients who cannot tolerate the compromising side effects of the tricyclic antidepressants and monoamine oxidase inhibitors.
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PMID:5-phenyl-2-furamidines: a new chemical class of potential antidepressants. 614 16


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