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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of cannabidiol (CBD) were compared to those produced by haloperidol in rats submitted to experimental models predictive of antipsychotic activity. Several doses of CBD (15-480 mg/kg) and haloperidol (0.062-1.0 mg/kg) were tested in each model. First, CBD increased the effective doses 50% (or) ED50 of apomorphine for induction of the sniffing and biting stereotyped behaviors. In addition, both CBD and haloperidol reduced the occurrence of stereotyped biting induced by apomorphine (6.4 mg/kg), increased plasma prolactin levels and produced palpebral ptosis, as compared to control solutions. However, CBD did not induce catalepsy even at the highest doses, in contrast to haloperidol. Such a pharmacological profile is compatible with that of an "atypical" antipsychotic agent, though the mechanism of action is uncertain and may not be identical to that of the dopamine antagonists.
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PMID:Effects of cannabidiol in animal models predictive of antipsychotic activity. 167 94

The potentiation of motor activity caused by ephedrine (Eph) in mice was inhibited by prazosin but not by sulpiride. This potentiation effect caused by apomorphine (Apo) was not inhibited by prazosin. Apo produced stereotyped behavior (including sniffing, licking, and biting) in rodents, but Eph was ineffective except at the toxic dose (400 mg.kg-1 in mice, 200 mg.kg-1 in rats). Apo antagonized haloperidol-induced catalepsy in mice whereas Eph had no such effect. Severe vomiting was evoked by Apo in dogs, but not by Eph even when lethal dose (20 mg.kg-1) was used. Palpebral ptosis induced by prazosin was abolished by intracerebroventricular injection of Eph in mice, but not affected by Apo. The results suggest that the central stimulating action of Eph is mediated by alpha 1-adrenoceptors and not by dopamine receptors.
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PMID:[Comparison of central stimulating effects between ephedrine and apomorphine]. 181 6

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

In an earlier preliminary study, manassantin A, a neolignoid from Saururus cernuus was found to show neuroleptic type activity in mice when given by the i.p. route. It blocked the stereotypy and hyperactivity caused by amphetamine at doses comparable to those of haloperidol, but unlike the latter, did not show catalepsy or ptosis at atoxic doses. In the present study, a more detailed comparison of manassantin A with haloperidol and in some cases with chlorpromazine and reserpine using a variety of neuroleptic parameters and by various routes of administration is described. Results of the present study clearly show that the drug is readily absorbed from various routes of administration and shows many of the patterns of neuroleptic activity. Manassantin A was comparable to haloperidol in many of the tests but unlike the latter, did not produce antiadrenergic or anticholinergic effects. Manassantin A was found to bind weakly to calf caudate membranes (IC50 3500 nM) while haloperidol (IC50 5 nM) and chlorpromazine (IC50 50 nM) inhibited [3H]haloperidol binding. Manassantin A also did not affect the dopamine-induced adenylate cyclase activity in rat caudate nuclei (IC50 greater than 10,000 nM) while haloperidol (IC50 700 nM) and chlorpromazine (IC50 350 nM) inhibited the enzyme synthesis. These biochemical and behavioral tests suggest that manassantin A exhibits a selective neuroleptic profile and may be considered to behave as an atypical agent.
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PMID:Further studies on the neuroleptic profile of manassantin A. 197 9

Effects of recombinant human Tumor Necrosis Factor (rHu-TNF, PT-050) administered s.c. and i.v. on the central nervous system were investigated behaviorally and physiologically in different animal species. With i.v. administration at doses of 10(4) U/kg and less, PT-050 produced no significant changes in most of behavioral and physiological tests, except that a transient increase in rectal temperature in dogs occurred with 0.765 x 10(4) U/kg and acetic acid-induced writhing syndrome in mice was inhibited with 10(4) U/kg. Locomotor activity in mice was inhibited after 3 x 10(4) U/kg. With 10(5) U/kg and more, in addition to the above effects, diverse effects were observed as follows: various symptoms were induced in general behavior in mice such as piloerection, catalepsy, lowering of body position, ptosis and pupil dilatation; rectal temperature was increased in rats and decreased in mice; cortical EEG was synchronized in hippocampal theta waves were disturbed in gallamine-immobilized cats. On the other hand, with s.c. administration, the effect on rectal temperature was seen at 10(4) U/kg in dogs and at 10(5) U/kg in rats. Cortical EEG in conscious rabbits was affected with 10(6) U/kg. At higher dose of 10(7) U/kg. PT-050 (s.c.) further influenced locomotor activity, rectal temperature and acetic acid-induced writhing syndrome in mice. However, even with 10(7) U/kg (s.c.), no effect was found in general behavior, rotarod performance and hexobarbital narcosis in mice. Thus, it is concluded that PT-050 has weaker effects on the central nervous system by s.c. route than by i.v. route. From the present findings and the efficacy of PT-050 as TNF, it is suggested that PT-050, when administered intratumorally, may be useful for cancer therapy without severe side effects.
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PMID:General pharmacology of recombinant human tumor necrosis factor. 2nd communication: effects on central nervous system functions. 233 65

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

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.
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PMID:[Behavioral pharmacological properties of the novel antidepressant paroxetine, a selective 5-HT uptake inhibitor]. 253 Jan 42

The hypothesis was tested that some of the effects in rats of the prototypical benzodiazepine, diazepam, would grow (i.e., sensitize) with the passage of time after acute administration as we had previously observed following stimulants, antidepressants, neuroleptics and other compounds. Our principal findings indicate that: 1) A single pretreatment with 0.5 mg/kg of diazepam significantly enhances the anticonvulsant effect of this same dose administered again two weeks later. 2) One injection of 2.5 mg/kg of diazepam significantly sensitizes the catalepsy and ptosis observed following the administration of haloperidol two weeks but not two hours later. These data provide the first evidence for time-dependent sensitization after benzodiazepines and perhaps by implication, of GABA neurons. They may also suggest that acute stimulation of GABA neurons triggers the progressive development of a long-term, antidopaminergic influence. Finally, they raise the question of whether the progressive anxiolytic influence seen during the first week or so of benzodiazepine therapy depends on the passage of time rather than repeated drug treatment.
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PMID:Anticonvulsant and other effects of diazepam grow with time after a single treatment. 257 Nov 70

A series of 3-phenyl-2-piperazinyl-5H-1-benzazepines and related compounds were synthesized and evaluated for potential neuroleptic activity. The preparation of these compounds was carried out by 2,3-dichlorination of 3-phenyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-ones with phosphorus pentachloride followed by amination and concurrent dehydrochlorination. Compounds having the 4-chloro or 4-fluoro substituent in the 3-phenyl group were found to possess the neuroleptic-like activity. Among them, 2-(4-methyl-1-piperazinyl)-3-(4-fluorophenyl)-5H-1-benzazepine dihydrochloride (23) was comparable to chlorpromazine in inhibiting exploratory activity, conditioned avoidance response, and self-stimulation response and more potent than chlorpromazine in antagonizing apomorphine-induced emesis. These neuroleptic effects may be based on an antidopaminergic property of the compound. In causing catalepsy or ptosis, however, 23 was weaker than chlorpromazine. Therefore, this ring system is of interest as a novel class of neuroleptics. Some compounds having the 7-chloro or 7-bromo substituent showed potent anticonvulsant effects against maximal seizures induced by electroshock or pentylenetetrazole.
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PMID:A novel class of potential central nervous system agents. 3-Phenyl-2-(1-piperazinyl)-5H-1-benzazepines. 289 53

Manassantin A (MNS-A), a novel dineolignan isolated from Saururus cernuus was evaluated for its central depressant effects. Intraperitoneal (IP) administration of MNS-A to mice at nontoxic doses caused a decrease in spontaneous motor activity and inhibition of amphetamine-induced stereotypy, with an ED50 of 0.21 +/- 0.02 mg/kg for its antiamphetamine activity. Doses of MNS-A up to the LD50 did not produce catalepsy and ptosis as were observed with haloperidol used as a reference drug. The compound caused a dose-dependent hypothermia, while haloperidol was not very effective in this test. Potentiation of pentobarbital-sleeping time was observed to be of comparable degree with both drugs. In spite of the higher toxicity (acute LD50 5.4 +/- 0.2 mg/kg, IP) than that shown by haloperidol, the somewhat selective neuroleptic profile of MNS-A makes it an interesting candidate for more detailed studies.
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PMID:Preliminary evaluation of manassantin A, a potential neuroleptic agent from Saururus cernuus. 289 91


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