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

Male Wistar rats, 35-days-old, maintained on a thiamine deficient diet for 30 days showed marked growth inhibition and a heart rate less than 70% of that of control rats. We examined the effect of thiamine deficiency on the action of drugs effecting the central nervous system at this period. In thiamine deficient rats treated with chloral hydrate 200 mg/kg, ketamine 100 mg/kg sodium pentobarbital 50 mg/kg, and hexobarbital 100 mg/kg, the sleeping time increased. Pretreatment with 15 mg/kg of the metabolic enzymes inhibitor, SKF-525A, 30 min prior to the hexobarbital administration resulted in prolongation of sleeping time in all groups. The thiamine deficient rats slept almost 3.5 times longer than did the control group. Pretreatment with 100 mg/kg of the metabolic enzyme inducer, sodium phenobarbital, 48 hours prior to hexobarbital treatment resulted in decreased sleeping time in all groups, as compared with only hexobarbital treatment. In the thiamine deficient rats the catalepsy and ptosis induced by the i.p. administration of tetrabenazine 50 mg/kg was reduced even when the control and pair-fed groups responded to this drug at the drug peak time. The spontaneous neuronal activity of lateral hypothalamus was most sensitive to the administration of 5-hydroxytryptophan in thiamine deficient rats.
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PMID:[The effect of thiamine deficiency on the actions of drugs affecting the central nervous system in rats (author's transl)]. 696 42

A series of 3-aryl-1,3-dihydrospiro[benzo[c]thiophene-1,4'-piperidine] derivatives was synthesized and evaluated pharmacologically for potential psychotropic activity. Potent antidepressant-like activity was noted throughout the series, as assessed by tetrabenazine (TBZ) ptosis prevention in mice and potentiation of 5-hydroxytryptophan (5-HTP) induced behavioral effects in rats. A possible therapeutic advantage of the title compounds appears to be the overall low anticholinergic potential in comparison with the classic tricyclic antidepressants. Several congeners with nuclear halogen substitution also exhibited CNS stimulant properties, as evidenced by their ability to induce a dopamine agonist-like stereotypy and to increase the spontaneous motor activity in mice.
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PMID:Novel tetracyclic spiropiperidines. 1. 3-Aryl-1,3-dihydrospiro[benzo[c]thiophene-1,4'-piperidines] as potential antidepressants. 697 Aug 18

A psychopharmacological profile of mesterolone, an androgen and potential antidepressant drug, was tested in mice and rats. Given in a dose of 80 mg/kg ip, mesterolone potentiated the action of L-DOPA in mice and in doses 40 and 80 mg/kg ip potentiated the amphetamine stereotypy in rats. On the other hand, in doses of 20--80 mg/kg ip mesterolone did not affect the reserpine induced hypothermia and ptosis, did not antagonize the apomorphine induced hypothermia in mice, did not change the motor stimulation produced by amphetamine and did not affect the spiperone induced catalepsy in rats. Mesterolone did not affect the head twitch response after 5-hydroxytryptophan in mice and was inactive in the behavioral despair test in rats. The results indicate that the psychopharmacological profile of mesterolone only slightly resembles the profile of classical imipramine-like anti-depressants.
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PMID:Psychopharmacological profile of mesterolone. 719 78

4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a mixture of cis- and trans-4-(dimethylamino)spiro[cyclohexane-1,1'(3'H)-isobenzofuran]-3'-ones (1a,b), which were separated by fractional crystallization. Addition of aryllithium or aryl Grignard reagents to 1a,b and formic acid reduction afforded cis- and trans-4-(dimethylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofurans] 3a-f, which were converted to secondary amine analogues 5a-e. Tentative stereochemical assignments are based on chemical arguments and are supported by 13C NMR chemical shift data. Marked inhibition of tetrabenazine-induced ptosis is a property of most antidepressants, and significant antitetrabenazine activity is observed for several of these compounds. Optimal antitetrabenazine activity is associated with the cis-3'-phenyl series, and the cis secondary amine 5a is approximately twice as potent as the cis tertiary amine 3a. The various compounds are relatively weak with respect to potentiation of L-5-hydroxytryptophan-induced seizures.
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PMID:Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 6. Synthesis, 13C NMR, and biological evaluation of cis- and trans-4-amino-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives. 724 20

Dexamisole antagonized the reserpine-induced hypothermia but was ineffective in the apomorphine-induced hypothermia in mice. It reduced ptosis produced by reserpine in mice but this effect was very weak. The effect of dexamisole on the amphetamine-induced hyperactivity depended upon the animal species. Dexamisole reduced the duration of immobility in the despair test in rats. It did not modify the 5-HTP-induced head twitch reaction in mice but produced stimulation of the hind limb flexor reflex in spinal rats. The latter effect was blocked by phenoxybenzamine but not by cyproheptadine and metergoline. Dexamisole also exerted a sedative and hypothermic effect. The above findings indicate that the pharmacological profile of dexamisole resembles in some respects that of tricyclic antidepressants; they also point out that this drug has a central noradrenergic activity.
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PMID:Psychopharmacological profile of dexamisole. 745 9

A series of 4,6-diaryl pyridazin-3-ones substituted in the 2-position by [4-(4-aryl piperazin-1-yl]-but-2-ynyl moieties was synthesized and evaluated for antidepressant activity. The structures of these new pyridazine derivatives were confirmed by IR, 1H-NMR spectra and by elementary analysis. At 150 mg/kg i.p., they induced little or no reduction of the duration of immobility of mice in the forced swimming test. Head twitches produced by L-5-hydroxytryptophan in mice pretreated with pargyline were significantly potentiated by most of the tested compounds. In addition, pyridazine derivatives did not antagonize reserpine-induced palpebral ptosis or enhance the toxic effects of yohimbine and were almost devoid of anticholinergic properties in mice.
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PMID:Synthesis of new serotonergic 2-substituted 4,6-diaryl pyridazin-3-ones. 748 10

The potential antidepressant effects of two pyridazine derivatives, 5-benzyl 6-methyl 2-[4-(3-trifluoro-methyl phenyl) piperazin-1-yl] methylpyridazin-3-one (PC4) and 5-benzyl 6-methyl 2-[4-(3-chlorophenyl) piperazin-1-yl] methylpyridazin-3-one (PC13), were evaluated using classical psychopharmacological tests in mice. The intraperitoneal LD50 values of PC4 and PC13 were respectively 1125.8 and 429.6 mg kg-1. Only at intraperitoneal doses of 100 mg kg-1 did PC4 or PC13 significantly decrease locomotor activity. Both compounds (5-20 mg kg-1, i.p.) reduced the duration of immobility of mice in the forces swimming test, antagonized reserpine (2.5 mg kg-1, i.p.)-induced ptosis, and potentiated reserpine (2.5 mg kg-1, i.p.)-induced hypothermia. PC4 and PC13 (20 mg kg-1, i.p.) partly reversed hypothermia induced by low dose apomorphine (5 mg kg-1, s.c.) but were less effective for higher doses of apomorphine (16 mg kg-1, s.c.). At 200 mg kg-1, intraperitoneal PC13 enhanced the toxic effects of yohimbine (30 mg kg-1, s.c.), while PC4 was inactive. Head twitches produced either by L-5-hydroxytryptophan (4 mg kg-1, i.p.) in mice pretreated with pargyline (100 mg kg-1, i.p.) or by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (3 mg kg-1, i.p.) were antagonized by both pyridazine derivatives (20 mg kg-1, i.p.). PC4 and PC13 showed analgesic properties in the phenylbenzoquinone-induced abdominal constriction test (5.0 < ED50 < 5.5 mg kg-1, i.p.) and in the hot-plate test (10 to 37% of analgesia at 10 mg kg-1, i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioural profile of two potential antidepressant pyridazine derivatives including arylpiperazinyl moieties in their structure, in mice. 760 73

Duloxetine is a dual inhibitor of norepinephrine and serotonin reuptake. Duloxetine (3.13-50 mg/kg p.o.) significantly prevented tetrabenazine (1 and 50 mg/kg s.c.)-induced ptosis in mice and rats. Moreover, duloxetine (1.56-12.5 mg/kg p.o.) also inhibited reserpine (1 mg/kg s.c.)-induced hypothermia in mice. When duloxetine (12.5-100 mg/kg p.o.) and 5-hydroxytryptophan (80 and 100 mg/kg i.p.), a precursor of serotonin, were administered simultaneously to mice and rats, head movement behavior and tremor were observed. In addition, duloxetine (25-100 mg/kg p.o.) significantly attenuated immobility in forced swimming in mice, as equally effective as commonly used antidepressant drugs. Duloxetine (12.5-25 mg/kg p.o.) significantly decreased rapid eye movement sleep and slow-wave deep sleep and increased the awake period, as shown in the rat EEG. However, duloxetine (25-200 mg/kg p.o.) did not affect salivation and lacrimation induced by oxotremorine (1 mg/kg s.c.), a cholinergic agonist, whereas it (25-50 mg/kg) reduced the oxotremorine-induced tremor in part. These results indicated that duloxetine produced behavioral and electroencephalographic responses resulting from the inhibition of norepinephrine and serotonin reuptake in vivo, and that it had a weak anticholinergic action. Therefore, duloxetine may be clinically useful as an antidepressant.
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PMID:Behavioral and electroencephalographic properties of duloxetine (LY248686), a reuptake inhibitor of norepinephrine and serotonin, in mice and rats. 789 17

Effects of beta-amyrin palmitate isolated from the leaves of Lobelia inflata were studied on the central nervous system of mice and were compared with those of antidepressant drugs, mianserin and imipramine. In the forced swimming test, beta-amyrin palmitate, like mianserin and imipramine, reduced the duration of immobility of mice significantly in a dose-dependent manner (5, 10 and 20 mg kg-1). beta-Amyrin palmitate (5, 10 and 20 mg kg-1) or mianserin (5, 10 and 20 mg kg-1) elicited a dose-related reduction in locomotor activity of mice and antagonized locomotor stimulation induced by methamphetamine. In contrast, imipramine (5, 10 and 20 mg kg-1) increased locomotor activity and potentiated methamphetamine-induced hyperactivity. beta-Amyrin palmitate showed no effect on reserpine-induced hypothermia, whilst mianserin (10 mg kg-1) and imipramine (10 and 20 mg kg-1) antagonized the reserpine-induced effect. Unlike imipramine, beta-amyrin palmitate and mianserin did not affect haloperidol-induced catalepsy, tetrabenazine-induced ptosis and apomorphine-induced stereotypy. beta-Amyrin palmitate and imipramine had no effects on the head-twitch response induced by 5-hydroxytryptophan, whereas mianserin (5, 10 and 20 mg kg-1) decreased it in a dose-dependent manner. A potentiating effect of beta-amyrin palmitate (5, 10 and 20 mg kg-1) on narcosis induced by sodium pentobarbitone was stronger than that of imipramine (10, 20 and 40 mg kg-1) but weaker than that of mianserin (2.5, 5 and 10 mg kg-1). These results suggest that beta-amyrin palmitate has similar properties in some respects to mianserin and might possess a sedative action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological properties of beta-amyrin palmitate, a novel centrally acting compound, isolated from Lobelia inflata leaves. 810 3

The novel benzodioxopiperazine, S 15535 (4-(benzodioxan-5-yl)1-(indan-2- yl)piperazine), displayed high affinity for 5-HT1A binding sites (1.8 nM) whereas its affinity was 100-fold lower at other 5-HT receptor types, at alpha 1, alpha 2- and beta-adrenoceptors and at dopamine D1 and D2 receptors. In vivo, S 15535 (0.16-10 mg/kg s.c.) acted as an antagonist at postsynaptic 5-HT1A receptors in completely blocking the flat-body posture and hypothermia elicited by the 5-HT1A receptor agonist, 8-OH-DPAT. It had no effect when applied alone. At presynaptic 5-HT1A receptors, S 15535 acted as an agonist in inhibiting striatal accumulation of 5-hydroxytryptophan (0.04-0.63 mg/kg s.c.) and in spiperone reversibly reducing electrical activity of the dorsal raphe nucleus (0.004-0.031 mg/kg i.v.). At doses up to 40.0 mg/kg s.c., S 15535 neither inhibited methylphenidate-induced gnawing nor elicited ptosis suggesting a lack of antagonist properties at, respectively, dopamine D2 receptors and alpha 1-adrenoceptors. In conclusion, S 15535 is a potent 5-HT1A ligand which acts, in vivo, as a highly selective agonist and antagonist at presynaptic and postsynaptic 5-HT1A receptors, respectively.
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PMID:S 15535: a highly selective benzodioxopiperazine 5-HT1A receptor ligand which acts as an agonist and an antagonist at presynaptic and postsynaptic sites respectively. 838 59


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