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

Piflutixol, 6-fluoro-9-[3-(4-(2-hydroxyethyl)piperidino)propylidene]-2-trifluoromethyl-thioxanthene, has been shown to have pronounced neuroleptic properties. It is a very potent inhibitor of methylphenidate-induced stereotypies in mice, amphetamine and apomorphine-induced stereotypies in rats, apomorphine-induced stereotypies and vomiting in dogs. Furthermore piflutixol causes cataleptic reaction in small doses and inhibits conditioned avoidance reaction in rats. The compound is equally potent orally and parenterally and has a prolonged effect. Piflutixol has up to the present proved to be the most potent inhibitor of dopamine-stimulated adenylate cyclase in rat striatum in vitro. Piflutixol has a stron sedative effect (inhibition of spontaneous motor activity, induction of ptosis and potentiation of barbiturate anaesthesia) and in addition inhibits reticular arousal reaction in very low doses. Thus piflutixol constitutes a unique combination of potent anti-stereotyped activity with potent sedative effects. This means that piflutixol may prove to be a low-dose basic neuroleptic with long duration of action.
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PMID:The pharmacology of a new potent, long acting neuroleptic, piflutixol. 57 63

GK 13 (N-[1-(2-benzo (b) thiophenyl)-cyclohexyl] piperidine), GBR 12783 (1-[2-(diphenylmethoxy)-ethyl] 4-(3-phenyl propenyl)-piperazine and dexamphetamine are three indirect catecholaminergic agonists, acting via different neurochemical mechanisms. We have compared their effects in rodents, in several behavioral tests. All three drugs increased locomotion. The stimulant locomotor effect of dexamphetamine was more easily antagonized by haloperidol than that of GBR 12783 and GK 13. Only dexamphetamine reversed reserpine-induced akinesia. This reversal was prevented by pretreatment with either GK 13 or GBR 12783. The three drugs reduced pentobarbital sleeping time in mice. They induced rotation ipsilateral to a unilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. The stereotypies induced by GK 13 and GBR 12783 were essentially limited to sniffing. Haloperidol-induced catalepsy was apparently more easily antagonized by dexamphetamine than by GK 13 or GBR 12783. GK 13 and GBR 12783 had no significant effects on body temperature. The three drugs displayed an anti-immobility effect in the "despair test". Dexamphetamine and GK 13 reversed the hypothermia induced by apomorphine (16 mg/kg), as well as reserpine-induced hypothermia and reserpine-induced ptosis. Dexamphetamine induced a dose-dependent anorectic effect, whereas GK 13 and GBR 12783 induced only a brief and partial anorexia. Similar observations were made on water intake. Pretreatment with either GBR 12783 or GK 13 did not affect the dexamphetamine-induced anorexia. Effects of the three drugs are discussed by reference to their known neurochemical properties on catecholaminergic transmission.
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PMID:Comparison of the effects of three indirect dopamine agonists, GK 13, GBR 12783 and dexamphetamine on behavioural tests involving central catecholaminergic transmissions. 197 95

Conditioning of behavioural effects produced by two drugs acting differently upon dopaminergic neurotransmission was studied. Nomifensine and the putative dopamine autoreceptor agonist B-HT 920 produce contrasting effects on motility, namely increases in locomotor activity and stereotypies as compared to hypokinesia and ptosis. The administration of each of these drugs (US) was repeatedly associated with well-defined environmental stimuli (CS): a wire cage associated with an auditory and on olfactory stimulus. The rats were conditioned for 7 days with 20 mg/kg nomifensine IP each day. After conditioning, the rats were treated with the solvent alone in presence of the CS. Not only did sniffing and licking occur, but also gnawing, even though the latter response was not evident after acute administration of the drug or during the conditioning period. Nomifensine (20 mg/kg IP) also acutely decreased the ratio of 3,4-dihydroxyphenylacetic acid/dopamine concentrations (DOPAC/DOPAMINE); this ratio was not altered in the conditioned rats, 60 min after solvent administration in presence of the CS. Rats were conditioned with 0.02 mg/kg IP B-HT 920 daily for 8 days. During the conditioning phase, akinesia and ptosis showed a slight enhancement and a faster onset. After conditioning, when the rats were treated with the solvent alone, the majority of them showed akinesia and/or ptosis during the observation period, in contrast to pseudoconditioned controls. When these rats were conditioned or pseudoconditioned, respectively, with B-HT 920 for further 5 days using 0.02 mg/kg again, treatment with the same dose in presence of the CS produced a significant enhancement and acceleration of these signs in conditioned as compared with pseudo-conditioned control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conditioning of behavioural signs produced by nomifensine and by B-HT 920 in rats. 282 15

We investigated whether pharmacological effects of the dopamine agonist apomorphine can be conditioned by establishing an association of apomorphine administration with exteroceptive cues. Apomorphine was repeatedly administered and subsequently, the rat was put into a test cage and exposed to an acoustic and an olfactory stimulus ("conditioned rats"). Control animals ("pseudoconditioned" rats) were treated with the same pharmacological schedule of apomorphine not temporally associated with the stimuli. On the test day, both groups were injected with saline and exposed to the stimuli described. The stereotyped behaviour produced by large doses of apomorphine (0.5 or 2.0 mg/kg SC), namely sniffing, licking and gnawing, could be conditioned in a pronounced way. During the conditioning period, a change in the stereotypies was observed with regard to the time-course (earlier occurrence) and to the character of the stereotypies (from sniffing to licking and gnawing), when 0.5 mg/kg apomorphine was used, but not with the dose of 2.0 mg/kg. The conditioned responses showed a relatively uniform distribution during the observation period with some increase towards the end of the observation period. Some signs produced by a low dose of apomorphine (0.07 mg/kg SC), namely hypomotility and ptosis, but not yawning, could also be conditioned, although in a less pronounced way. An intermediate dose of apomorphine (0.18 mg/kg SC) produced both signs observed after large doses and those observed after a small dose, occurring alternatingly. Both types of signs could be conditioned using this dosage. Conditioning did not alter striatal or mesolimbic dopamine turnover.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conditioning of pre- and post-synaptic behavioural responses to the dopamine receptor agonist apomorphine in rats. 302 94

1. Benzyleugenol (BE), a phenylpropene derivative, protects rats and mice against maximal electroshock seizures and has a protective index superior to that of phenobarbital. The present paper describes experiments carried out to further characterize the pharmacological and toxicological profile of this compound. 2. BE, at a dose range of 100-400 mg/kg ip, was inactive when tested for the following effects: analgesia, as measured by the hot plate and acetic acid writhing methods; neuroleptic-like effects, when tested by the catalepsy and palpebral ptosis, conditioned avoidance response and apomorphine-induced stereotypies methods; and anxiolytic effects, measured by the shock-elicited aggressiveness of mice. In contrast, tolerance to the anticonvulsant effect of BE, at dose range of 240-800 mg/kg orally, developed in mice and rats after 10 to 40 days of continued treatment. 3. BE, at dose range of 104-800 mg/kg orally, proved to be remarkably safe when chronically administered to laboratory animals. Thus, 3 to 6 month administration of large BE doses to rats and mice did not affect body weight, behavioral measures, serum and blood tests, or hematological parameters. Anatomopathological examinations of viscera of BE-treated animals did not reveal alterations which could be attributed to drug treatment. 4. Daily treatment up to 3 months of male rats and mice with BE, at a dose range of 80-800 mg/kg orally, did not affect the reproductive capacity of the animals. Pregnant females treated with BE during different periods of gestation gave birth to litters similar to those of control females; when adult, BE and control litters performed equally well in a passive avoidance task. 5. These results were compared with those of known anti-epileptic drugs, such as phenytoin, phenobarbital and valproic acid, and it is suggested that BE deserves further research as a potential candidate for the treatment of epilepsy.
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PMID:Pharmacological and toxicological profile of benzyleugenol, a phenylpropene derivative possessing anticonvulsant properties. 333 Jun 76

Interactions between the direct (unconditioned) behavioural effects apomorphine and its conditioned effects after pairing with previously neutral stimuli were studied. Rats were injected once daily for 3-12 times, with apomorphine (2.0 mg/kg or 0.5 mg/kg or 0.07 mg/kg s.c. the dose kept constant in each series), in the presence of defined environmental stimuli (a wire cage in association with an acoustic and an olfactory stimulus) as conditional stimuli. The two larger doses produced stereotyped sniffing, licking, and gnawing, the smallest dose akinesia, ptosis, yawning and penile erections. During the conditioning phase, the drug produced most of the effects with increasing intensity and in the case of the stereotypies, there also was a shift to higher scores of stereotypy, with a reduced latency in onset of the signs. On the test day, 1 day after the last administration of apomorphine, the conditioned rats as well as "pseudoconditioned" controls were treated with a test dose of apomorphine in the presence of the conditional stimuli. Pseudoconditioned rats had been treated with the same pharmacological schedule of apomorphine and had the same familiarity with the stimuli, but both were kept separate. A test dose of 0.5 mg/kg of apomorphine produced stereotypies with a significantly higher score and shorter latency in onset in conditioned than in pseudoconditioned rats. Rats conditioned with the lowest dose showed a significantly longer total duration and a shorter latency in onset of akinesia and ptosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on interactions between conditioned and unconditioned behavioural responses to apomorphine in rats. 362 83

The effects of enantiomers of nomifensine were compared in five psychopharmacological tests in which (+/-)-nomifensine is active. In mice, (+)-nomifensine increased motor activity at 16 mg/kg, 8 mg/kg reduced the hypothermia and ptosis induced by reserpine and antagonized the hypothermia induced by 16 mg/kg of apomorphine. (+)-Nomifensine 4 mg/kg potentiated yohimbine toxicity. (-)-Nomifensine 4,8, or 16 mg/kg was inactive in all these tests. In rats, (+)-nomifensine 8 mg/kg induced stereotyped movements whereas (-)-nomifensine 64 mg/kg did not produce stereotypies.
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PMID:Psychopharmacological effects of nomifensine enantiomers. 404 12

Lippia multiflora (L.m.) is a verbenacea used in Congo as conventional tea decoction. No traditional indication is known in this country. Nevertheless, in Ghana the plant is used for the treatment of arterial hypertension. The aim of this study is to investigate the psychotropic activity of the aqueous extract of L.m. using the classical tests of experimental psychopharmacology. The extract of L.m. is constituted by lyophilisated powder obtained from an infusion of dried leaves. Different doses are prepared: 200, 400, 600, 800, 1,000 and 1,200 mg/kg dissolved in 1 ml of NaCl 0.9%. L.m. is administered by intraperitoneal or oral route. The wistar rats of both sexes, weighing between 150-200 g, are used. Animal's behaviour is observed macroscopically. The spontaneous motor activity is appreciated by using the number of squares crossed by animal with the four paws in ten minutes (Martin and al. method slightly modified). The rectal temperature is measured. The effect of L.m. on stereotypies induced by apomorphin and anesthesia induced by phenobarbital are studied. The traction test is used to investigate the muscle relaxant effect of L.m. and analgesic activity is evaluated by using acetic acid and hot plate methods by comparison with diazepam 2 and 4 mg/kg. Fischer-t test is used for the statistical analysis of results. L.m. is well tolerated by rats. No mortality is observed with the doses used. So the doses of 200, 400 and 600 mg/kg were selected for experiments. At theses doses L.m. caused: a precocious ataxia, a sedation, a ptosis and a yellow coloration of urines, these effects are dose dependent; a significant reduction of spontaneous motor activity: control 61.60 +/- 6.48, L.m. 200: 16.40 +/- 5.68 (P < 0.01), L.m. 400: 12.20 +/- 2.01 and L.m. 600: 9.60 +/- 1.90 (P < 0.01); no modification of rectal temperature and apomorphin stereotypies; a reduction of sleep latence: control 22.40 +/- 1.89 min, L.m. 200: 17.20 +/- 2.74 min (P < 0.01), L.m. 400: 13.80 +/- 1.81 min (P < 0.01) and L.m. 600: 13.40 +/- 2.16 min (P < 0.01); a potentiation of phenobarbital anesthesia: L.m. 200: 209.80 +/- 29.58 min (N.S.), L.m. 400: 336.40 +/- 22.23 min (P < 0.01), L.m. 600: 342.20 +/- 16.28 min (P < 0.01) and control: 199.40 +/- 2.90 min; an increase at the dose of 400 mg/kg of the time necessary for the restoration of the paws to the metallic bar in the traction test: control; 0.8 +/- 0.1 s, L.m. 400: 7.04 +/- 2.29 s (P < 0.05); a reduction of abdominal cramps induced by acetic acid. This number is respectively 18.40 +/- 4.49 (P < 0.05); 15.00 +/- 2.90 (P < 0.01), 14.20 +/- 3.89 (P < 0.01), 11.60 +/- 4.75 (P < 0.01), 13.00 +/- 2.00 (P < 0.01) and 33.80 +/- 5.04 for L.m. 200 mg/kg, L.m. 400 mg/kg, L.m. 600 mg/kg, Diazepam 2 and 4 mg/kg and control; an increase of reaction time on the hot plate: L.m. 200: 3.26 +/- 0.46 s (N.S.), L.m. 400: 4.50 +/- 0.80 s (P < 0.01), L.m. 600: 10.50 +/- 1.56 s (P < 0.001), diazepam 2 mg/kg: 2.90 +/- 0.51 s (N.S.), diazepam 4 mg/kg: 5.90 +/- 1.09 s (P < 0.01) and control 2.10 +/- 0.26 s. Those results demonstrated that L.m. possess a tranquilizer and analgesic activities as Diazepam. But, anticonvulsant and anxiolytic tests are necessary to confirm the psychopharmacological profile of this medicinal plant.
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PMID:[Psychopharmacologic properties of Lippia multiflora]. 985 Aug 19