Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The neuronal effects of the anthelmintic piperazine (Pip) on rat sympathetic ganglia were studied in vitro by means of intracellular and extracellular recording techniques. 2. Surface potential recordings indicated that Pip (0.1-10 mM as citrate, 1-30 mM as hexahydrate) produced a sustained depolarization (reversible on washing) of rat ganglia. gamma-Aminobutyric acid (GABA, 1-100 micro M) also evoked reversible depolarizations but, unlike Pip, responses to the higher doses of GABA declined during a 2 min exposure. Depolarizations produced by Pip or carbachol (but not GABA) were markedly depressed by hexamethonium but only slightly by bicuculline or picrotoxin. 3. Intracellular recordings revealed that Pip-induced depolarizations were accompanied by an increase in membrane conductance and a broadening and depression of the directly-evoked spike. 4. In the presence of hexamethonium (1 mM), the responses to Pip hexahydrate and to cholinoceptor agonists were abolished, but Pip citrate still changed the spike configuration and induced membrane hyperpolarization with a small conductance increase. These residual effects were mimicked by superfusing with Na citrate or Ca2+-free medium, suggesting that significant Ca2+ binding by the citrate anion of the Pip salt was probably responsible for the observed activity of Pip citrate in the presence of hexamethonium. 5. It is concluded that on rat ganglia Pip is a nicotinic agonist, with no detectable GABA-mimetic activity.
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PMID:The effects of piperazine on rat sympathetic neurones. 731 92

The effect of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, was studied in the forced-swimming test, a model of depression, in mice. Fluvoxamine at 60 mg/kg, p.o. significantly decreased the immobility time in the forced-swimming test. A similar effect was observed by the selective norepinephrine reuptake inhibitor desipramine at the same dose. Furthermore, the suppression of immobility time was slightly potentiated by repeated administration of fluvoxamine, and a significant effect was observed at 30 mg/kg, p.o. The effect of fluvoxamine on forced-swimming was unaffected by the 5-HT2 antagonist ritanserin. On the other hand, the 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine) potentiated the effect of fluvoxamine on forced-swimming. It is expected, however, that a 5-HT1A antagonist should antagonize the effect of fluvoxamine when 5-HT1A mediates the suppressive effect of fluvoxamine on the immobility time in forced-swimming. From these results, neither the 5-HT1A- nor the 5-HT2-receptor subtype is involved in the suppressive effect of fluvoxamine on the immobility associated with forced-swimming.
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PMID:Neither the 5-HT1A- nor the 5-HT2-receptor subtype mediates the effect of fluvoxamine, a selective serotonin reuptake inhibitor, on forced-swimming-induced immobility in mice. 749 85

The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists. The results, together with our previous findings, indicate an apparent rank order of potency: 5-carboxamidotryptamine (5-CT) > sumatriptan > methysergide > 5-HT >> 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) > 5-methoxytryptamine (5-MeOT) = 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) > alpha-methyl-5-hydroxytryptamine (alpha-Me 5-HT) >> (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The equipotent molar ratios were 5-CT 0.12, sumatriptan 0.4, methysergide 0.72, 5-HT 1.0, 8-OH-DPAT 13.3, 5-MeOT 26.7, TFMPP 31, alpha-Me 5-HT 402 and DOI > 3333. Time for peak depression from start of agonist application was 3-4 min for 5-HT, 5 min for sumatriptan and 5-MeOT, 5-7 min for alpha-Me 5-HT and 12 min for 8-OH-DPAT. The half-time for recovery from peak depression was 1.5 +/- 0.3 min for 5-HT, 2.8 +/- 0.3 min for 5-MeOT, 5.3 +/- 1.5 min for sumatriptan, 13 +/- 2.9 min for 8-OH-DPAT and > 30 min for alpha-Me 5-HT. 8-OH-DPAT induced depression of the reflex (IC50 0.85, 0.7-1.0 microM, geometric mean and 95% confidence limits) was blocked by spiperone (1 microM, apparent pA2 6.3) suggesting mediation via 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A novel 5-HT receptor or a combination of 5-HT receptor subtypes may mediate depression of a spinal monosynaptic reflex in vitro. 796 10

Spontaneous spreading depression episodes were studied in CA1 and CA3 areas of immature hippocampal slices (two to 30 days postnatally) during 4-aminopyridine (50 microM) perfusion. Spreading depression occurred in the CA3 area of 34% of all slices tested (two to 30 days postnatally). The duration and frequency of the spreading depression field potentials changed with development. In the CA3 area, their duration decreased from 169 +/- 22 s (n = 17, postnatal days to to 10) to 55 +/- 7 s (n = 10, postnatal days 21-30), their rate of occurrence increased from four episodes per hour (0.0011 +/- 0.0001 Hz, n = 11, postnatal days two to 10) to 6.5 episodes per hour (0.0018 +/- 0.0003 Hz, n = 8, postnatal days 21-30), while their amplitude remained stable (10-30 mV). Spreading depression d.c. potential shift originated closer to CA1 than CA3. Furthermore, spreading depression field potentials had greater magnitude (amplitude and duration) in CA1. Spreading depressions were reversibly blocked by the N-methyl-D-aspartate receptor antagonist 3,3-(2-carboxy-piperazine-4-yl)-propyl-1-phosphonate (CPP, 1-5 microM, n = 15), but were not affected by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX, 2-5 microns, n = 11), which is a non-N-methyl-D-aspartate receptor antagonist. The GABAA receptor antagonist bicuculline methiodide (3-10 microM) initially favored and then blocked spreading depression in 79% of the slices tested (n = 16). In addition, bicuculline impaired spreading depression propagation from CA1 to CA3. 4-Aminopyridine also induced the appearance of other types of spontaneous activity, such as ictal and interictal-like epileptiform discharges. The effects of 3,3-(2-carboxy-piperazine-4-yl)-propyl-1-phosphonate, 6-cyano-7-nitro-quinoxaline-2,3-dione and bicuculline on epileptiform activity were opposite to those on spreading depression. Our findings demonstrate that spreading depression can occur as early as two days postnatally and that the characteristics of this phenomenon change with maturation. These results also indicate that 4-aminopyridine-induced spreading depression episodes and epileptiform activity are mediated by the activation of different types of excitatory amino acid receptors. Finally, spreading depression is influenced by blockade of the GABAA receptor.
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PMID:4-Aminopyridine-induced spreading depression episodes in immature hippocampus: developmental and pharmacological characteristics. 810 81

Bilateral infusion of 5-hydroxytryptamine (5-HT) agonists into the substantia nigra pars reticulata (SNr) of awake rats was shown to influence oral behavior. The 5-HT1A agonist (R)-8-hydroxy-2-(di-propylamino)- tetralin (8-OH-DPAT) (1.3-13 nmol on each side) produced a dose-dependent depression of vacuous chewing movements (VCMs) that lasted about 20 min. The (R)-8-OH-DPAT-induced depression of VCMs was blocked by the simultaneous intranigral infusion of a specific 5-HT1A antagonist [(-)-(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin HCl (UH-301)], which had no effect when given alone. Another 5-HT1A agonist [(5-methoxy-N,N-dimethyltryptamine hydrogen oxalate (5-MeO-DMT)] also reduced VCM frequencies. Intranigral infusion of the nonspecific 5-HT-agonists 1-(3-triflouro-methylphenyl) piperazine (TFMPP) and 1(m-chlorophenyl)-piperazine (mCPP) and a 5-HT3 agonist [2-methyl-5-hydroxytryptamine (2-Me-5-HT)] increased VCM after 5- to 10-nmol doses. Another 5-HT3 agonist (1-phenylbiguanide) and a 5-HT2 agonist [1-(4-bromophenyl-2,5-dimethoxy)-2-aminopropane (DOB)] had no significant effect. As most 5-HT receptors in the SNr are of the 5-HT1B subtype, these results suggest that the increased VCM frequency was mediated via nigral 5-HT1B receptors. The importance of 5-HTergic mechanisms in the development of drug-induced dyskinesias is discussed.
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PMID:Modulation of oral movements by intranigral 5-hydroxytryptamine receptor agonists in the rat. 826 98

The effects of the thiadiazinone derivative, 5-[1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydrochinolin-6-yl]-6-met hyl-3,6- dihydro-2H-1,3,4-thiadiazin-2-on (EMD 53998), and of its (+)EMD 57033 and (-)EMD 57439 enantiomers, were tested on the contractile properties and cytosolic [Ca2+] ([Ca2+]i) transients of single intact guinea pig cardiac myocytes. Cells were loaded with the ester form of the fluorescent probe, indo-1, and bathed in a N-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid-buffered solution at 25 degrees C (1 mM of CaCl2, 1 Hz stimulation rate). All three substances exerted a pronounced increase in twitch amplitude: the maximal effect of the racemate (380% of control value) was approximately the sum of the effects of its two enantiomers (186 and 236% of control value for the (+)- and (-)-enantiomer, respectively). The [Ca2+]i transient, measured as the 410-to-490 nm indo-1 fluorescence ratio transient after excitation, was increased by the racemate and its (-)-enantiomer (172 and 152% of control value, respectively), but was not increased by the (+)-enantiomer. The racemate and the (-)-enantiomer, but not the (+)-enantiomer, markedly reduced the contraction duration and [Ca2+]i transient duration. In unstimulated cells resting length was significantly reduced by the (+)-enantiomer, and this was accompanied by a decrease in indo-1 fluorescence; the (-)-enantiomer had no effect on either parameter. In the presence of 2,3 butanedione monoxime (BDM), which markedly reduces twitch amplitude by inhibiting cross-bridge mechanics, addition of the (+)-enantiomer restored the twitch contraction to above the pre-BDM level without augmenting the [Ca2+]i transient. In contrast, the (-)-enantiomer failed to reverse the BDM-induced contractile depression, even though it caused a significant increase of the [Ca2+]i transient. Thus, in intact cells the positive inotropic effect of EMD 53998 is due to specific properties of its enantiomers: the (-)-enantiomer has adenosine 3',5'-cyclic monophosphate-like effects (increase in amplitude and reduction of [Ca2+]i transient and contraction durations), whereas the (+)-enantiomer enhances the myofilament-Ca2+ interaction.
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PMID:Enantiomeric dissection of the effects of the inotropic agent, EMD 53998, in single cardiac myocytes. 838 21

The effects of acute (2 days) and repeated (21 days) administration (50 mg/kg in the diet) of the selective serotonin (5-HT, 5-hydroxytryptamine) reuptake inhibitor, citalopram, on extracellular levels of 5-HT and their modulation by terminal autoreceptors in the hypothalamus of freely moving rats were compared in vivo by microdialysis. When studied without washout, extracellular levels of 5-HT were increased by both acute and repeated citalopram administration. In rats treated repeatedly, extracellular 5-HT levels were 43% (but not significantly) greater than in those treated acutely. Extracellular levels of 5-HT in control and citalopram-treated rats were similar when measured after 24 h washout. The enhancing effect of non-selective serotonergic autoreceptor antagonists, methiothepin (100 microM) or 1-(1-naphthyl)piperazine (NP) (10 microM), administered through the microdialysis probe, after 24 h washout, was similar in both control and chronically treated groups. These results suggest that repeated administration of citalopram followed by a washout of 24 h does not lead to desensitization of the terminal autoreceptor as measured in vivo in contrast to the effects we have shown previously in vitro. In rats treated chronically with citalopram without washout, methiothepin had a greater maximal effect on 5-HT outflow in comparison to rats receiving acute citalopram treatment. This finding suggests that a 5-HT autoreceptor antagonist or a combination of such a drug with a 5-HT uptake inhibitor would produce a greater increase of extracellular levels of 5-HT in hyposerotonergic states such as depression.
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PMID:Effects of acute and repeated administration of citalopram on extracellular levels of serotonin in rat brain. 872 May 83

It has been suggested that in vivo formation of the metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) may be a major drawback in the use of buspirone as an anti-anxiety agent. To test this hypothesis, the effects of buspirone, alone or with proadifen (an inhibitor of liver microsomal enzymes) pretreatment, were contrasted with those of 1-PP in the murine elevated plus-maze test of anxiety. At 3.0 mg/kg (but not lower doses), buspirone per se had modest anxiolytic-like effects (increased percentage of open arm entries; reduced stretched-attend postures and flatback approach) that were associated with increased grooming and immobility. However, in proadifen-pretreated mice, buspirone produced behavioural depression only, with marked effects evident both at 1.0 and 3.0 mg/kg. As proadifen blocks the biotransformation of buspirone to 1-PP, these data suggest that any anxiolytic activity of buspirone in the murine plus-maze may be attributable to its principal active metabolite. Consistent with this hypothesis, 1-PP (0.5-13.5 mg/kg) produced dose-dependent anti-anxiety effects on both conventional and ethological measures that were not confounded by motoric impairment. Results are discussed in relation to biochemical and electrophysiological studies suggesting that 1-PP has a direct action at 5-HT1A receptors.
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PMID:Comparative behavioural profiles of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) in the murine elevated plus-maze. 929 74

We examined the effects of (R)- and (S)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) on the monosynaptic spinal reflex in rats. In intact rats, (R)-8-OH-DPAT (10 microg/kg, i.v.) enhanced the amplitude of the monosynaptic reflex, whereas at 100 microg/kg, it reduced the amplitude. (S)-8-OH-DPAT enhanced the monosynaptic reflex dose-dependently. In spinalized rats, (R)-8-OH-DPAT produced dose-dependent inhibition, but the (S)-enantiomer did not affect the monosynaptic reflex. Pretreatment with spiroxatrine or 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190) inhibited (R)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did 5-hydroxytryptamine (5-HT) depletion. Ketanserin reduced the effect of (R)-8-OH-DPAT. These pretreatment regimens had no effect on the monosynaptic reflex depression produced by the (R)-enantiomer in intact and spinalized rats. Pretreatment with prazosin inhibited (S)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did noradrenaline and 5-HT depletion. These results suggest that supraspinal 5-HT1A receptors and the descending serotonergic system are involved in the stimulatory effect of (R)-8-OH-DPAT on the monosynaptic reflex, while both the descending serotonergic and noradrenergic systems, the latter acting via alpha1-adrenoceptors, are involved in the effect of the (S)-enantiomer on this reflex.
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PMID:Differential effects of (R)- and (S)-8-hydroxy-2-(di-n-propylamino)tetralin on the monosynaptic spinal reflex in rats. 1041 36

Rats were given a single dose of reserpine (5 mg/kg s.c.) and behavioural responses to agonists at 5-HT receptor subtypes compared with those of control animals 21 days later. The following effects of activating postsynaptic 5-HT1A receptors by the agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) were significantly increased: tail-flick, reciprocal forepaw treading, flat body posture. The hyperphagic effect of activating presynaptic 5-HT1A receptors by 8-OH-DPAT tended to increase and hypothermia on activating postsynaptic 5-HT1A sites tended to decrease. The hyperlocomotor effect of activating 5-HT1A sites also tended to decrease possibly as a result of a dependence of this response on the known depletion of catecholamines by reserpine. Head shakes on activating 5-HT2A receptors by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and two effects of activating 5-HT2C receptors by 1-(3-chlorophenyl) piperazine (mCPP) were significantly increased (hypophagia, anxiety) and a third effect, hypolocomotion tended to increase but hypophagia on activating postsynaptic 5-HT1B receptors by CP-94, 253 was significantly attenuated. The results are discussed with particular reference to altered 5-HT function in depression.
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PMID:Effect of reserpine on behavioural responses to agonists at 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor subtypes. 1046 92


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