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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 central action of the potential antidepressant drug pizotifen (Sandomigran) was studied in mice, rats and rabbits. Pizotifen in doses up to 10 mg/kg i.p. was ineffective in classic tests for antidepressant activity. It neither antagonized the effects of reserpine in rats (hypothermia, ptosis) nor potentiated the effects of amphetamine (in mice and rats), nialamide or L-dopa (in mice) on locomotor activity. However, its antidepressant activitiy was found in the 'despair test' in rats. On the other hand, pizotifen inhibited the head twitch reaction induced by L-5-hydroxytryptophan in mice (ED50 = 0.009 mg/kg, i.p.) and by 5-methoxytryptamine (+ tranylcypromine) in rats (ED50 = 0.45 mg/kg, i.p.). It also antagonized tryptamine-induced clonic convulsions of fore-paws in rats (ED50 = 0.35 mg/kg, i.p.), and in doses of 5--10 mg/kg s.c. inhibited hyperthermia produced by LSD in rabbits. Finally, pizotifen (0.1--0.3 mg/kg, i.v.) inhibited or abolished LSD- or quipazine-induced stimulation of the hind limb flexor reflex of spinal rats; the above effect was not due to noradrenolytic action of the drug. These results suggest that pizotifen strongly blocks the central postsynaptic serotonin receptors.
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PMID:The central action of pizotifen. 11 Dec 96

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

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, 5.2, and 10.8 mg/kg respectively). It counteracts convulsions induced by tryptamine in rats (ED50=3.75 mg/kg). Trazodone abolishes hyperthermia induced by serotoninomimetics (LSD, quipazine, fenfluramine) in rabbits. It does not affect ptosis induced by reserpine, and diminishes stimulation of the locomotor activity induced by amphetamine. Our findings demonstrate that trazodone has a central antiserotonin action, similarly as three other antidepressant drugs: mianserin, danitracen and doxepin, whose central antiserotonin action has been found previously.
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PMID:On the central antiserotonin action of trazodone. 48 64

Compound WA-335 (9,10-dihydro-10-(-1-methyl-4-piperidylidene)9-anthrol) was studied with regard to its antidepressant and central antiserotonin action in mice and rats. WA-335 depresses reserpine-induced hypothermia, particularly in mice, but does not affect ptosis induced with this neuroleptic. The compound diminishes spontaneous motility in mice and rats, including mice stimulated with amphetamine. WA-335 acts synergistically with amphetamine in which it potentiates stereotyping and enhances motility. The compound has no influence on the action of L-DOPA and does not alter hypothermia or increase motility induced with this amino acid. WA-335 does not affect the drop in body temperature or stereotype induced with apomorphine. In mice, WA-335 inhibits motility elicited with L-5-hydroxytryptophan, and in rats as well as mice prevents occurrence of head-twitches due to activation of serotonin neurons. The compound has no effect on the righting reflex abolished with fenfluramine in frogs, and given together with reserpine slightly counteracts abolition of this reflex. WA-335 raises the level of serotonin in the brains of rats, and lowers the level of 5-hydroxyindoleacetic acid. In addition, WA-335 exhibits cholinolytic activity and abolishes the symptoms elicited with oxotremorin in mice and rats.
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PMID:The action of compound WA-335 on the central nervous system. 94 51

With its chronic administration in a dose of 100 mg/kg lithium carbonate inhibited shaking of the head induced in mice with 5-hydroxytryptophan (5-HTP). This effect did not differ from the action following a single injection of lithium, when the interval between injection of lithium and of 5-HTP was one hour. With the interval lengthened to 24 hours the frequency of shaking diminished only under the effect of chronic administration. At the 5th, 10th and 21st day of a daily administration lithium failed to produce any effect on the hypothermal action of a reserpine-like agent Po 4-1284, but would reduce the protective action of imipramine in a ptosis test. A single injection of lithium made against the background of a chronic injection of water produced an opposite effect, viz. it significantly reduced the protective action of imipramine in hypothermia, but did not affect it with reference to ptosis. Hence, chronic administration of lithium leads to potentiation in its action of the serotonin-negative and central adreno-negative componets and to extenuating the peripheral adreno-negative component.
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PMID:[Effect of lithium on the central serotonin- and adrenergic processes after its chronic administration]. 108 64

Some central effects of Ro 19-6327--a new MAO-B inhibitor--were studied in mice and rats. Given in low doses (1 or 3 mg/kg) Ro 19-6327 did not affect the locomotor activity of mice but its high dose (10 mg/kg) increased the activity. In rats Ro 19-6327 inhibited the locomotor activity but the effect was not dose dependent and not always significant. Ro 19-6327 did not change the locomotor activity in mice induced by L-DOPA (plus benserazide--an inhibitor of peripheral decarboxylase). The drug suppressed the reserpine-induced hypothermia and ptosis in mice and partly counteracted the apomorphine-induced hypothermia. It markedly enhanced (10 mg/kg) the amphetamine-induced stereotypy in rats. L-5-Hydroxytryptophan (L-5-HTP)-induced head twitch response was unchanged by Ro 19-6327. The drug given three times was inactive in forced swimming test. Repeated treatment with Ro 19-6327 (twice daily for 14 days) produced the enhancement of (+)-amphetamine- and nomifensine-induced hyperactivity in rats. Unlike a number of antidepressants, Ro 19-6327 did not potentiate the clonidine aggressiveness in mice, but--in contrast--inhibited it. The results suggest that Ro 19-6327 given repeatedly produces no changes in the responsiveness of the alpha-adrenergic system (in references to effects mediated by alpha 1-adrenoceptors). Adaptive changes in dopamine system are doubtful.
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PMID:Central effects of Ro 19-6327 given acutely and repeatedly. 166 12

Behavioural effects on dopaminergic transmission of a phenylindane derivative, Lu 19-005 [(+/-)-trans-3-(3,4-dichlorophenyl)-N-methyl-l-indanamine, HCI], with potent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake in rats and the effect on DA, NA and 5-HT activity in mice have been studied and compared with those of other known DA, NA and 5-HT uptake inhibitors with different selectivity ratios. Lu 19-005 induced stereotyped behaviour after parenteral and oral administration with a duration of action of more than 24 h. The stereotyped licking and biting induced by Lu 19-005 was antagonized by reserpine and cis(Z)-flupentixol, but not affected by prazosin, p-chlorophenylalanine and alpha-methyl-p-tyrosine pretreatments. Metergoline slightly facilitated the onset of stereotypy. Lower doses of Lu 19-005 induced ipsilateral circling in unilaterally 6-hydroxy-DA-lesioned rats. Finally, Lu 19-005 antagonized the catalepsy induced by perphenazine. In mice, Lu 19-005 potentiated the apomorphine-induced gnawing, reversed tetrabenazine-induced ptosis and potentiated the behavioural effects of 5-HTP within a similar dose range. The effects of Lu 19-005 were compared with those of other reference compounds. Nomifensine had qualitatively similar effects in rats although of much shorter duration. In mice, nomifensine selectively reversed tetrabenazine-induced ptosis. Weaker effects in all test models were found with bupropion, LR 5182 and GBR 13.069, compounds with inhibitory effect on DA and NA uptake. The DA-, NA- and 5-HT-uptake inhibitor diclofensine, however, had no effect in rats except in the 6-hydroxy-DA-circling test and had low potency in mice. The specific 5-HT- and NA-uptake inhibitors citalopram and talsupram, respectively, were ineffective in all rat models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacology in vivo of the phenylindan derivative, Lu 19-005, a new potent inhibitor of dopamine, noradrenaline and 5-hydroxytryptamine uptake in rat brain. 240 54

McN-5652 is one of a series of substituted pyrrolo-isoquinolines that, as a group, potently inhibit the uptake of one or more of the monoamines, norepinephrine, serotonin and dopamine. McN-5652 is characterized by exceptionally high potency as an inhibitor of the uptake of serotonin by rat brain synaptosomes in vitro (Ki approximately 0.6 nM) and ex vivo (ED50 approximately 2 mg/kg p.o.). The high potency of McN-5652 as a serotonin uptake inhibitor in vivo is indicated further by the low doses required to potentiate L-5-hydroxytryptophan-induced head twitches in mice (ED50 = 0.4 mg/kg 2 hr after p.o. dosing) and the serotonin syndrome in rats (ED50 = 1.5 mg/kg 2 hr after p.o. dosing). McN-5652 also potently inhibited the synaptosomal uptake of norepinephrine (Ki approximately 3 nM) and was a moderately potent inhibitor of the synaptosomal uptake of dopamine (Ki approximately 40 nM). McN-5652 inhibited tetrabenazine-induced ptosis in rats and mice but was much less effective in blocking the sedation caused by tetrabenazine. In rats, McN-5652 did not induce the stereotyped behavior often caused by dopamine agonists and inhibitors of dopamine uptake. Receptor binding experiments indicated that McN-5652 has a weak affinity for serotonin 5-HT2 and alpha-1 adrenergic receptors (apparent Ki approximately 200 nM) and a very low affinity for dopamine D1 and D2 receptors, serotonin 5-HT1, alpha-2 adrenergic, muscarinic and gamma-aminobutyric acid-A receptors. Experiments using the guinea pig ileum indicate that McN-5652 is a weak, noncompetitive antagonist of histamine.
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PMID:McN-5652: a highly potent inhibitor of serotonin uptake. 290 1

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


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