Abstract:
:1. To investigate the role of nitric oxide in epilepsy we have studied the effects of agents which affect nitric oxide synthesis in sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone (GEP) rats. 2. The neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole (7-NI) is anticonvulsant in these models with ED50 values against clonic seizures in mg kg-1 i.p. (times following injection) of: 74 (+0.25 h), 120 (+1 h) in DAB/2 mice, and 56 (+0.25 h), 42 (+0.5 h), 36 (+1 h), 28 (+2 h), 38 (+4 h), 93 (+8 h) in GEP rats. 3. Therapeutic indices (locomotor deficit ED50/anticonvulsant ED50) for 7-NI are low, ranging from 0.6 to 1.1 at +0.25 h to +1 h after administration in GEP rats, but are more favourable at later times (1.6 at +2 h and 2.9 at +4 h). 4. The substrate for nitric oxide synthase, L-arginine (500-5000 mg kg-1, i.p. or 100-300 micrograms, i.c.v.) but not D-arginine (300 micrograms i.c.v.) is anticonvulsant in DBA/2 mice. L-Arginine (500-5000 mg kg-1, i.p. or 1800-6000 micrograms, i.c.v.) is a more potent anticonvulsant than D-arginine (1500-2500 mg kg-1, i.p. or 6000 micrograms, i.c.v.) in GEP rats. 5. In DBA/2 mice, L-arginine (30 micrograms i.c.v.) reverses the anticonvulsant effect of 7-NI (50 mg kg-1, i.p.). 6. In GEP rats, low dose L-arginine (25-50 mg kg-1, i.p.) but not D-arginine (50 mg kg-1, i.p.) reverses the anticonvulsant effect of low dose 7-NI (25 mg kg-1, i.p.). A higher dose of L-arginine (500 mg kg-1, i.p.) or 7-NI (50 mg kg-1, i.p.) produces summation of anticonvulsant effect. 7. The product for nitric oxide synthase, L-citrulline (250-831 micrograms i.c.v.), is convulsant in DBA/2 mice. 8. The anticonvulsant effect of the neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole, may therefore be mediated by L-arginine accumulation, as well as by a reduction in nitric oxide and L-citrulline formation in rodent models of reflex epilepsy.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Smith SE,Man CM,Yip PK,Tang E,Chapman AG,Meldrum BSdoi
10.1111/j.1476-5381.1996.tb15690.xsubject
Has Abstractpub_date
1996-09-01 00:00:00pages
165-73issue
1eissn
0007-1188issn
1476-5381journal_volume
119pub_type
杂志文章abstract::1. Imidazoline binding sites have been reported to be present in the locus coeruleus (LC). To investigate the role of these sites in the control of LC neuron activity, we studied the effect of imidazolines using in vivo and in vitro single-unit extracellular recording techniques. 2. In anaesthetized rats, local (27 pm...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0702255
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1984.tb16225.x
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2013-03-01 00:00:00
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更新日期:1975-05-01 00:00:00
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更新日期:2017-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:1997-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15353.x
更新日期:1996-04-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:1982-02-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1987.tb10295.x
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doi:10.1038/sj.bjp.0706193
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journal_title:British journal of pharmacology
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更新日期:1998-11-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2008-08-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2000-06-01 00:00:00
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更新日期:1998-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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journal_title:British journal of pharmacology
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更新日期:2018-03-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2010-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1998-08-01 00:00:00
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更新日期:2020-02-01 00:00:00