Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:The action of compound WA-335 on the central nervous system. 94 51

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.
 ...
PMID:Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities. 97 78

The behavioral effects of lopramine [N-methyl-N-(4-chlorobenzoyl-methyl)-3-(10, 11-dihydro-5H-dibenz (b,f) azepin-5-yl) propylamine hydrochloride] were investigated in mice and rats and compared with those of amitriptyline and imipramine. Lopramine inhibited reserpine hypothermia and haloperidol catalepsy in mice and tetrabenazine ptosis in rats. In addition the drug potentiated the effects of methamphetamine, and DOPA- or apomorphine-induced stereotypy in mice, whereas it suppressed muricide of the rat induced by either olfactory bulbectomy or delta9-tetrahydrocannabinol, similar to the responses seen with imipramine and amitriptyline. On the other hand,lopramine increased spontaneous motor activity and markedly potentiated methamphetamine hyperactivity. In contrast to imipramine and amitriptyline, lopramine failed to counteract both the lethal effect of physostigmine and oxotremorine tremor in mice, indicating that the drug had no central anticholinergic effect. Lopramine, even at such a large dose as 5,000 mg/kg p.o., caused neitherimpairment of coordinated motor activity nor muscle relaxation. It is concluded that lopramine is a new type of tricyclic antidepressant with extremely low toxicity and without central anticholinergic action.
 ...
PMID:[Behavioral pharmacology of a new antidepressant, lopramine]. 103 9

The effect of maprotiline (N-methyl-9, 10-ethanoanthracene-9 (10H)-propylamine) on animal behavior was investigated in mice and rats and compared with those of amitriptyline and imipramine. Maprotiline inhibited reserpine hypothermia in mice and tetrabenazine ptosis in rats, while it potentiated the effects of methamphetamine, L-DOPA and apomorphine in mice, in a similar manner to that of amitriptyline and imipramine. Maprotiline was more potent than anitriptyline and imipramine in antagonizing haloperidol-induced catalepsy as well as in suppressing muricide induced by either olfactory bulbectomy or delta-9-tetrahydrocannabinol in rats. Maprotiline potentiated anesthesia induced by thiopental or ether in mice to a lesser degree than did amitriptyline, and failed to counteract the lethal effect of physostigmine or oxotremorine tremor in mice, indicating that this drug has no central anti-cholinergic effect. Maprotiline markedly inhibited hyperemotionality of the rat with either septal lesions or olfactory bulb ablations, suggesting that it does have a tranquilizing effect. Inhibition of conditioned avoidance response of the rat in the shuttle box and reduction of methamphetamine group toxicity with maprotiline were similar to those with amitriptyline. Maprotiline exaggerated pentetrazol convulsion, decreased muscle tone and impaired coordinated motor activity in mice to a much lesser degree than amitriptyline and imipramine. LD50 of maprotiline was approximately twice that of imipramine and three times that of amitriptyline. These results indicate that maprotiline is a new type of antidepressant, has a low toxicity and shares both potent antidepressant and some tranquilizing effect, without possessing central anticholinergic action.
 ...
PMID:[Behavior pharmacology of maprotiline, a new antidepressant]. 124 Aug 30

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.
 ...
PMID:Central effects of Ro 19-6327 given acutely and repeatedly. 166 12

The natural history and response to different treatments were assessed in 31 consecutive patients with blepharospasm (BS) and/or oromandibular dystonia (OMD). The mean age at onset was 52.4 years and there was a female preponderance of 2.5 to 1. Ocular symptoms preceded the onset of blepharospasm in more than 50% of the affected patients, whereas psychiatric and dental problems prior to the onset of focal dystonia were found in 10% and 13% of the cases respectively. Dystonia elsewhere, mainly in the craniocervical area, was found in 23% of patients and appeared to follow a somatotopic progression. The first 2-3 years of history were crucial for the spread of dystonia to other face and body parts. When OMD was the first symptom, a lower tendency of dystonia to progress elsewhere was observed. A putative cause was found in 14% of patients who showed clinical and radiographic evidence of basal ganglia or rostral brainstem-diencephalon lesions. The response to different drugs was inconsistent although transient improvement was induced by haloperidol in 6 patients, by L-Dopa plus deprenyl in 3 patients, by trihexyphenidyl in 2 patients and by clonazepam in 2 patients. One, apparently spontaneous, remission was observed. Botulinum A toxin was injected in the orbicularis oculi of 8 patients affected by BS: moderate to marked improvement lasting 5 to 30 weeks (mean 14.5 weeks) was achieved in all cases; transient ptosis, lasting 1 to 3 weeks, occurred in 3 cases.
 ...
PMID:Facial dystonia: clinical features, prognosis and pharmacology in 31 patients. 251 66

The behavioral effects of paroxetine were investigated in mice and rats in comparison with imipramine and amitriptyline. 1) Locomotor activities were decreased by imipramine and amitriptyline but not by paroxetine in both animal species. 2) Paroxetine antagonized methamphetamine-induced hyperactivity in mice as did imipramine and amitriptyline. 3) Paroxetine showed a more potent antimuricidal effect in raphe-lesioned rats than imipramine and amitriptyline, and it also inhibited muricide in olfactory bulbectomized rats. 4) The immobility of rats in the forced swimming test was markedly decreased by imipramine and amitriptyline, but only slightly by paroxetine. 5) Like imipramine and amitriptyline, paroxetine potentiated the methamphetamine- or L-DOPA-induced stereotyped sniffing, and it inhibited oxotremorine-induced tremor. 6) Paroxetine antagonized reserpine-induced hypothermia, tetrabenazine-induced ptosis, and enhanced ether-induced anesthesia, all less potently than imipramine and amitriptyline. 7) The analgesic action of paroxetine was stronger than that of imipramine and amitriptyline. 8) Paroxetine did not antagonize maximal electroshock- or pentetrazol-induced convulsions and haloperidol- or THC-induced catalepsy in rats. In addition, paroxetine neither exerted muscle relaxation nor affected the shuttle-box type conditioned avoidance in rats. From these results, the behavioral effects of paroxetine, as compared with imipramine and amitriptyline, were characterized by its potent antimuricidal action in raphe-lesioned rats and its weak effect in the forced swimming test and by its less potent muscle relaxant, anticonvulsant, anticataleptic and anesthesia-potentiating actions.
 ...
PMID:[Behavioral pharmacological properties of the novel antidepressant paroxetine, a selective 5-HT uptake inhibitor]. 253 Jan 42

A potential antidepressant activity of B-193 was studied in mice and rats. In in vitro studies B-193 did not affect the uptake of NA and 5-HT. In in vivo models the tested compound did not influence the reserpine-induced hypothermia, hypoactivity and ptosis, the stimulating action of L-DOPA, the apomorphine-induced hypothermia. On the other hand, it produced a positive effect in the despair test. When given repeatedly, it evoked adaptive changes in brain neurotransmitter receptors, i.e. it decreased the density of beta-adrenoceptors and increased the number of alpha 1 ones; those changes were accompanied with functional alternations in the reactivity of those receptors: an attenuated behavioral reaction to salbutamol and enhanced aggressiveness induced by a high dose of clonidine. Furthermore, B-193 administered repeatedly enhanced hyperlocomotion induced by amphetamine but did not influence the stereotypy induced by apomorphine. These results indicate that B-193 possesses properties characteristic for atypical antidepressants.
 ...
PMID:Antidepressant profile of 9-methyl-2[-3-(4-phenyl-1-piperazinylpropyl)]-1,2,3,4-tetrahydro-beta- carbolin-1-one (B-193). 263 91

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.
 ...
PMID:[Pharmacological properties of MO-8282, a novel antidepressant]. 379 61

Experiments on cats revealed an emotiotropic action of melanostatin on the original spectrum of emotional reactivity, similar to the effects of L-DOPA and amantadin. The drug does not possess an antidepressant action proper but activates the aggressive-defensive behaviour in experimental reserpine depression and reduces the provocation-induced aggressive behaviour in experimental haloperidol depression. In reserpinized mice, it antagonizes reserpine hypothermia, increases muscle tone and eliminates ptosis. It decreases haloperidol-induced catalepsia. Melanostatin increases the brain level of dopamine and its metabolite, homovanilic acid.
 ...
PMID:[Psychopharmacologic spectrum of melanostatin]. 610 96


1 2 Next >>