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  • 1
    Electronic Resource
    Electronic Resource
    Clomethiazole (ZENDRA, CMZ) improves hind limb motor function and reduces neuronal damage after severe spinal cord injury in rat (1999)
    Springer
    Acta neuropathologica 98 (1999), S. 22-30 
    Details
    ISSN: 1432-0533
    Keywords: Key words Clomethiazole ; Rat ; Spinal cord-injury ; Neuroprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clomethiazole (CMZ) has a neuroprotective effect in experimental focal and global forebrain ischemia. This neuroprotective effect may depend on its ability to enhance GABA receptor activity. We have studied the effect of pretreatment with CMZ on motor function recovery and nerve cell damage after spinal cord injury (SCI). Rats were randomized and 30 min before SCI they received a single intraperitoneal dose of CMZ (150 mg/kg) or saline. The spinal cord was injured with a 50 g (4.5 g/mm2) load, applied over the exposed dura, through a curved rectangular plate (2.2 × 5.0 mm) for 5 min at T8–9. The animals became paraplegic 1 day after injury. The rats were evaluated for recovery of hind limb motor function. All animals recovered to some extent over the observation period of 12 weeks. However, hind limb motor function was significantly better in the animals pretreated with CMZ. At 12 weeks the rats were killed and perfused/fixed for morphological investigations. Microtubule-associated protein 2 (MAP2) immunostaining was used to stain neurons and dendrites and Luxol-fast blue to stain myelinated tracts of the white matter. The injured segment of the spinal cord showed severe atrophy, distortion, cavitation and necrosis of grey and white matter. Compared to uninjured controls the transverse sectional area was reduced to 32.7 ± 4% in untreated animals but only to 38.5% ± 4.1 in CMZ-treated animals. MAP2 staining showed that, compared to uninjured controls, grey matter was reduced to 7.4 ± 2.7% in saline-treated injured animals and to 22.7 ± 5.4% in CMZ-treated rats. Our results thus show that in this model CMZ improves hind limb motor function and attenuates the morphological damage to the spinal cord.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051047
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  • 2
    Electronic Resource
    Electronic Resource
    Is clozapine an (partial) agonist at both dopamine D1 and D2 receptors? (1998)
    Springer
    Psychopharmacology 138 (1998), S. 213-214 
    Details
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050665
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  • 3
    Electronic Resource
    Electronic Resource
    Factorisations for partition functions of random Hermitian matrix models (1996)
    Springer
    Communications in mathematical physics 179 (1996), S. 25-59 
    Details
    ISSN: 1432-0916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics , Physics
    Notes: Abstract The partition functionZ N , for Hermitian-complex matrix models can be expressed as an explicit integral over ℝ N , whereN is a positive integer. Such an integral also occurs in connexion with random surfaces and models of two dimensional quantum gravity. We show thatZ N can be expressed as the product of two partition functions, evaluated at translated arguments, for another model, giving an explicit connexion between the two models. We also give an alternative computation of the partition function for theφ 4-model. The approach is an algebraic one and holds for the functions regarded as formal power series in the appropriate ring.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02103715
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  • 4
    Electronic Resource
    Electronic Resource
    Two selective 5-HT1A receptor antagonists, WAY-100 635 and NDL-249, stimulate locomotion in rats acclimatised to their environment and alter their behaviour: a behavioural analysis (1998)
    Springer
    Psychopharmacology 139 (1998), S. 300-310 
    Details
    ISSN: 1432-2072
    Keywords: Key words Locomotion ; Rearing ; Activity ; NDL-249 ; WAY-100 635 ; 8-OH-DPAT ; 5-HT1A receptor ; Grooming ; Vacuous chewing ; Observation ; 5-HT1A receptor agonist ; 5-HT1A receptor antagonist ; DA-5-HT interaction ; SCH-23390 ; Raclopride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim was to study firstly, the motor effects of a new 5-HT1A antagonist, NDL-249 [(R)-3-(N-cyclopentyl-N-propylamino)-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxamide hydrochloride] and of the reference 5-HT1A antagonist WAY-100 635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride], in comparison to the 5-HT1A agonist (±)-8-OH-DPAT [(8-hydroxy-2-(di-N-propylamino) tetralin, hereafter 8-OH-DPAT], in rats acclimatised to the automated activity cages; secondly, to study whether the behavioural effects of NDL-249 and 8-OH-DPAT are sensitive to the 5-HT depleting effects of p-chlorophenylalanine (PCPA); thirdly, to characterise the nature of the antagonist-induced activation seen in the automatic activity cages with the aid of a behavioural observation analysis; fourthly, to examine the interaction between the 5-HT1Areceptors mediating the behavioural effects and dopamine (DA) receptors. NDL-249 was found to bind in vitro to rat hippocampal 5-HT1A receptors with high affinity and selectivity. In second messenger studies, it was devoid of agonist-like effects. In the locomotor activity studies, each antagonist significantly increased the incidence of horizontal activity, peripheral activity and rearing. 8-OH-DPAT, while significantly increasing peripheral and horizontal activities, decreased the incidence of rearing. PCPA blocked the motor effects of NDL-249 but did not affect those of 8-OH-DPAT. Observational analyses indicated that NDL-249 induced significant increases at one or more doses in sniffing, rearing and locomotion together with a significant reduction in stillness. WAY-100 635 significantly increased the incidence of rearing, intense grooming and vacuous chewing. The significant increases in sniffing, grooming and intense grooming and the significant decrease in stillness induced by the DA D1 agonist, SK&F 38393 [(±)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride], were not altered by concomitant pre-treatment with NDL-249. Pre-treatment of rats with either the DA D1 antagonist SCH-23390 (2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) or the DA D2 antagonist, raclopride, blocked the reduced stillness and increased sniffing and rearing induced by NDL-249. In conclusion, 5-HT1A antagonists including the new selective antagonist, NDL-249, induce mild behavioural activation in rats, which is mediated probably indirectly via DA systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050721
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  • 5
    Electronic Resource
    Electronic Resource
    Time course of bromocriptine induced excitation in the rat: behavioural and biochemical studies (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1995), S. 146-155 
    Details
    ISSN: 1432-1912
    Keywords: Key words Bromocriptine ; Dopamine autoreceptors ; Dopamine D1 receptors ; Dopamine D2 receptors ; Motor depression ; Motor stimulation ; Dialysis ; Neurotransmitter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to further investigate the behavioural and biochemical pharmacology of the directly acting dopamine (DA) receptor agonist bromocriptine (BRC). BRC produced an initial depression of locomotion followed after about an hour by a weak but significant locomotor stimulation. The stimulation was potentiated by concomitant administration of the D1 agonist SKF38393. Ex vivo biochemical determinations indicated that reductions in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels occurred in the striatum after BRC injection without a significant change in DA levels, indicating a reduced DA turnover. An increase in 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) levels occurred in the striatum leading to a significant increase in turnover (i.e. ratio of 5HIAA to 5HT). Noradrenaline concentrations increased in the striatum. In the cortex, sharp falls in HVA and DOPAC levels without a corresponding change in DA were observed. While there was no significant change in noradrenaline levels in this brain region, an increase in 5HIAA, but not in 5HT, levels occurred. These changes indicate an increase in 5HT turnover (ratio of 5HIAA to 5HT). In vivo dialysis indicated that extracellular levels of DA, DOPAC and HVA in the striata of freely moving rats were sharply reduced for at least 6 h after injection. In vitro binding studies showed that BRC exhibited high (Ki values in low nanomolar range) affinities for DA D2A, D2B, D3, α1 and α2 adrenergic receptors together with unexpectedly high affinity (about 1 nM) for 5HT1A receptors. The data indicate that the initial behavioural depression and later locomotor stimulation induced by BRC are accompanied by a sharp monophasic fall in striatal extracellular DA levels as indicated by dialysis studies. Since the behavioural stimulation was augmented by concomitant D1 receptor stimulation, the data suggest that the reduced DA turnover is influencing the amount of DA available to stimulate postsynaptic D1 receptors. However, the biochemical studies indicated that BRC has a high affinity for 5HT1A receptors and affects the turnover of 5HT in the brain. Thus, the behavioural effects of BRC may depend not only on effects on the DA system but also on 5HT systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169328
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