Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

R 18 503 (alpha-(p-chlorophenyl)-beta,beta-dimethylimidazole-1-ethanol) 40 mg/kg IP produced a mean of 168 (SEM +/- 4) wet shakes in the 35 min following its administration to 100 g male Wistar rats. No other behavioural abnormalities were seen at this dose. The wet-shakes were not caused by reduced body temperature. However, 20-30 min after R 18 503, body temperature was significantly elevated in comparison with saline treated controls. This supports a role for wet-shakes in thermogenesis in the rat, but suggests that R 18 503-induced wet-shakes are not adapted towards the maintenance temperature homeostasis. R 18 503-induced wet-shakes were potently antagonized by 5 narcotic analgesics, but not by aspirin-like drugs. A further 18 non-narcotic compounds including putative serotonin antagonists, neuroleptics and compounds thought to act on the alpha-adrenergic system, also antagonized R 18 503-induced wet-shakes. Spectral map analysis showed a close link between ED50-values of the non-narcotic R 18 503 wet-shake antagonists and their ED50's to antagonize noradrenaline-induced lethality; this was further confirmed by a highly significant Spearman Rank correlation between the two tests (rs = 0.77, p less than 0.001). However, the spectral mapping and Spearman correlation analysis showed no relationship between antagonism of R 18 503-induced wet-shakes and antagonism of apomorphine-induced stereotypy, tryptamine-induced bilateral forepaw clonus, mescaline-induced head twitches, and 5 HT-induced contractions of rat caudal artery. It is postulated that R 18 503-induced wet-shakes result from an interaction between the opiate system and the alpha-adrenergic system.
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PMID:Neuropharmacological profile of R 18 503-induced wet-shake behavior in the rat: noradrenergic and opiate components. 629 29

The effect of flunarizine (FLU) and sodium valproate (SV) alone and in combination were examined for their effects on seizure thresholds elicited by cortical stimulation in conscious rats. Two different pharmacodynamic parameters could be distinguished viz, the threshold for localised seizures (TLS) defined as the current (mu A) required to elicit forelimb clonus and the threshold for generalised seizure (TGS), defined as the current (mu A) required to elicit vigorous clonic activity without a tonic component. In preliminary neuro-behavioral studies on rats, the most favourable combination was FLU 10 mg/kg i.p. and SV 200 mg/kg i.p., which produced anticonvulsant efficacy with minimal neurotoxicity. With FLU alone, SV alone and the combination of FLU and SV, the mean % change +/- SEM from baseline values over a period of 6 h were for TLS: 3.8 +/- 0.8, 23.9 +/- 3.7, and 29.8 +/- 2.1; and for TGS 5.5 +/- 0.7, 15.6 +/- 2.7 and 190.9 +/- 22.7 respectively, indicating that FLU alone had no effect on TLS or TGS, SV significantly elevated TLS but had no effect on TGS and the combination of FLU plus SV produced a synergistic elevation of both TLS and TGS-the intensity of effect being more on TGS than on TLS. This model provides a new dimension to the profiling of two anticonvulsant agents with different mechanisms of anticonvulsant activity and offers predictive criteria for protective effects on clinical manifestations of partial or generalised tonic clonic seizure.
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PMID:Synergistic effect of flunarizine and sodium valproate on seizure thresholds elicited by cortical stimulation in conscious rats. 951 92