Convulsant activity

Nevertheless, RR is clearly a non-competitive antagonist that blocks the channel pore [2] with no effect on [ H]RTX binding [4]. RR was useful in dissecting responses mediated by capsaicin-sensitive nerves in vitro, but its use in animals was severely restricted by the toxicity (e.g. convulsive activity) that it caused [1]. 

PCP produced electrical seizure activity at 12.8 mg/kg IV, EEG spectra were clearly different from those produced by lower doses in that fast-frequency, high-amplitude EEG waves occurred and resulted in a spectral peak at about 15 Hz. EEG activity from 0 to 35 Hz occurred during seizures in contrast to subseizure doses, which produced EEG with little activity beyond 10 Hz. Generally, these seizures occurred immediately after IV injections and lasted 1 to 3 minutes. Similar spectra were obtained with NsBPCA (12.8 mg/kg), SKF-10,047 (25.6 mg/kg), and even with ketamine despite the absence of overt convulsant activity. Motor manifestations of EEG seizure activity included whole body tremors and vigorous twitches of the face and vibrissae. 

Rotarod, Righting Reflex, Convulsant Activity, and Lethality... 

There were no large differences in the symptomatology between animals pretreated with PHY+SCO or with PYR. On the other hand, animals pretreated with PHY+PC did not show convulsive activity as was found in the animals treated with the other scenarios. In some cases the post-intoxication therapy was even not necessary. 

The chronic oral MRL was based on a NOAEL of 0.025 mg/kg/day for convulsions in dogs administered endrin in the diet for 2 years (Kettering 1969). Concentrations of 0.05 and 0.1 mg/kg/day were associated with convulsive activity, slight to moderate vacuolization of hepatic cells, and occasional slight increases in liver weights. Other studies have reported hepatotoxicity in animals treated orally with endrin (Hassan etal. 1991 Treon et al. 1955). 

N-Alkylamino carbazoles (e.g., 494 and 495) possess significant anti-convulsant and diuretic activity. Introduction of an aminopropyl chain at the N-atom seems to enhance the anti-convulsant activity in combination with methoxy groups at positions 2, 3, and 4, or a chlorine atom at the C-2 and C-3 positions (458). 

Angel A, Rogers KJ. 1972. An analysis of the convulsant activity of substituted benzenes in the mouse. Toxicol Appl Pharmacol 21 214-229. 

Like morphine, meperidine has an active metabolite, normeperidine, formed by A-demethylation of meperidine. Normeperidine is not analgesic but is a proconvulsant and a hallucinogenic agent. For this reason, meperidine use in patients with renal or fiver insufficiency is contraindicated because of the decreased clearance of the drug and its metabolite. Convulsant activity has been documented in elderly patients given meperidine and in patients using PCA who have decreased renal function. 

Anti-convulsant activity. Methanol (50%) extract of the dried leaf, administered to mice, was active vs leptazol-induced convulsions . Ethanol (70%) extract of the fresh leaf, administered intraperito-neally to mice of both sexes at variable doses, was active vs metrazole- and strychnine-induced convulsions . Anti-estrogenic effect. Aqueous extract of the dried leaf smoke, administered to female adults at a concentration of 25.0 pL/plate, was active on granulosa cells. Results significant atp < 0.001 level . 

Caspers H, Speckmann EJ Cerebral P02, PC02 and pH changes during convulsion activity and their significance for spontaneous arrest of seizures. Epilepsia 13 669-725, 1972... 

Isoflurane has no epileptogenic potential in humans and there is no clinical or EEG evidence of convulsive activity during isoflurane... 

C-5 Large aliphatic groups >7 carbons Greater activity shorter duration convulsant activity... 

Montanine alkaloids are members of the alkaloids of the plant family of Amarylli-daceae. They represent a relatively small class of compounds with the typical methanomorphanthridine skeleton exhibiting some anxiolytic, anti-depressive and anti-convulsive activities [135, 136]. The total syntheses of the natural (-)-mon-tanine enantiomers are only mentioned, not described, here (for these (—(-enantiomers see, e.g. literature cited in [137]). 

Although these experiments analyzed the hypothesis that convulsant activity is required for the antidepressant-like effects of ( + )BW373U86, it did not thoroughly address the question of whether seizure activity is required for the antidepressant-like effects of delta opioid agonists. The benzodiazepine midazolam was demonstrated to inhibit seizure activity [49,50] however, seizure activity was not directly measured in the study by Broom et al. [35]. Interestingly, limited work has been done with the seizure activity of delta opioid agonists. One study demonstrated that the delta opioid agonist... 

Figure 1 The convulsive (a) and antidepressant-like (b) effects of SNC80 administered by intravenous injection infused in 20 sec. During and immediately after the infusion, rats were observed for 20 min to watch for convulsive activity (a). Thirty minutes after the SNC80 infusion, rats were evaluated in the forced swim test (b). Counts of immobility were recorded as previously described [62]. P <. 01 as compared to vehicle by Dunnett s post hoc test.

Calderon and Kenner Rice developed a series of compounds based on the structure of BW373U86. The chiral methylether derivative SNC-80 showed greater selectivity for the delta opioid receptor, but was apparently associated with a brief single episode of convulsant activity, seeming to indicate potential limitations in the therapeutic value of delta receptor agonists. Structurally similar compounds that did not bind to the delta receptor were also shown to produce similar convulsant activity, confusing the issue of whether convulsant activity was an effect associated with the delta receptor itself, or with the specific structure. 

For cyclohexane derivatives, convulsive activity is associated, apparently specifically, with a particular molecular topography that is only achieved with the aaaeee arrangement of substituents However, the norbornene and camphene carbon skeletons apparently permit the attainment of a similar topography... 

Both 3-amino-l-methyl-5 -pyrido[4,3-6]indole and 3-amino-l,4-dimethyl-5//-pyrido[4,3-ijindole were found to possess potent convulsant activity <90Mi 706-oi>. 

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