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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 284 (1974), S. 319-337 
    ISSN: 1432-1912
    Schlagwort(e): Diazepam ; Chlorpromazine ; Benzoctamine ; Spinal Cord ; GABA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effect of diazepam on several activities of the spinal cord was investigated in decerebrate and high-spinal cats by recording neurograms from lumbosacral ventral and dorsal roots and by measuring the levels of γ-aminobutyric acid (GABA) in the lumbosacral spinal cord. Chlorpromazine and benzoctamine were included for comparison with diazepam in part of the investigation. Diazepam depressed but did not abolish monosynaptic and polysynaptic ventral root reflex (VRR) responses; it was 3 to 5 times more potent in the decerebrate than in the spinal cat. Spontaneous gamma fibre activity was markedly and almost equally reduced by diazepam in both preparations. Dorsal root potentials (DRP's) and the presynaptic inhibition of monosynaptic VRR's elicited by stimulation of peripheral afferents were enhanced and prolonged by diazepam to the same extent in spinal and decerebrate animals; however, the enhancement of DRP's elicited by stimulation of the medullary reticular formation required approximately 3 time higher doses of diazepam. The effect of diazepam on presynaptic inhibition and DRP's was antagonized by bicuculline in a surmountalbe manner. Following amino-oxy-acetic acid (AOAA), which more than doubled the levels of endogenous GABA in the spinal cord, presynaptic inhibition and DRP's were enhanced but the amplitude of monosynaptic VRR responses was unaffected; diazepam further enhanced presynaptic inhibition and DRP's but no longer depressed monosynaptic VRR responses. Thiosemicarbazide, which decreased the level of GABA in the spinal cord by about 60%, reduced presynaptic inhibition and DRP's and prevented the augmenting effect of diazepam on these parameters. Doses of the organic solvent of diazepam in the 10 times higher amounts than used in the experiments with diazepam had only negligible and short-lasting effects; it seems very unlikely that the solvent contributed appreciably to the effect of diazepam solutions. It is concluded that 1) diazepam affects various activities of the spinal cord predominantly by a spinal site of action, 2) normal levels of GABA in the spinal cord seem to be a prequisite for the augmenting effect of diazepam on presynaptic inhibition in the spinal cord, 3) diazepam may act by altering the metabolism or disposition of GABA. Whether the enhancement of presynaptic inhibition fully accounts for the depressant effect of diazepam on monosynaptic and polysynaptic VRR's and on the gamma activity cannot be decided yet. In contrast to diazepam, chlorpromazine and benzoctamine did not enhance DRP's. Chlorpromazine depressed monosynaptic and polysynaptic VRR's and gamma activity only in the decerebrate cat. Benzoctamine was approximately as potent as diazepam in depressing monosynaptic and polysynaptic VRR responses in both preparations and in reducing gamma fibre activity in decerebrate cats, but was less potent than diazepam on the gamma fibre activity in spinal animals.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 300 (1977), S. 199-203 
    ISSN: 1432-1912
    Schlagwort(e): Kainic acid ; N-methyl-d-aspartate ; Glutamate receptor ; Aspartate receptor ; (-)-Nuciferine ; Glutamate antagonist ; Spinal cord
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Kainic acid (a rigid conformational analogue of glutamate), N-methyl-d-aspartate (the methylated derivative of aspartate), and (-)-nuciferine (an aporphine alkaloid with a depressant effect on glutamate-induced neuronal firing), which, so far, have been examined in microiontophoretic studies, were investigated in spinal cats for their effects on some spinal cord activities after intravenous injections. At low doses, kainic acid (0.3 mg kg−1) enhanced segmental monosynaptic but not polysynaptic ventral root reflexes and increased the excitability of motoneurones, whereas N-methyl-d-aspartate (3 mg kg−1) facilitated polysynaptic but not monosynaptic reflexes. Higher doses of the two amino acids depolarized motoneurones and primary afferent endings, enhanced monosynaptic reflexes and depressed polysynaptic reflexes. (-)-Nuciferine (1–10 mg kg−1) depressed monosynaptic but not polysynaptic ventral root reflexes in a dose-dependent manner and antagonized the effects of kainic acid but not of N-methyl-d-aspartate on the spinal cord. The results are consistent with the hypothetical excitatory transmitter role of glutamate in primary afferents and of aspartate in excitatory spinal cord interneurones; the findings also suggest that (-)-nuciferine may be used as a systemically effective, rather selective blocker of central glutamate receptors.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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