Anticonvulsant properties

The anticonvulsant primidone (1035) resembles phenobarbital but lacks the 2-oxo substituent. It was introduced in 1952 and has remained a valuable drug for controlling grand mal and psychomotor epilepsy. As might be expected, primidone is metabolized to yield phenobarbital (1034 X = 0) and C-ethyl-C-phenylmalondiamide (1036), both of which have marked anticonvulsant properties however, primidone does have intrinsic activity and an appropriate mixture of its metabolites has only a fraction of its activity (73MI21303). Primidone may be made in several ways, of which desulfurization by Raney nickel of the 2-thiobarbiturate (1034 X = S) or treatment of the diamide (1036) with formic acid (at 190 °C) seem to be the most satisfactory (54JCS3263). 

In 1960, the sedative, muscle-relaxing and anticonvulsant properties of 7-chloro-tV-methyl-5-phenyl-3//-l, 4-benzodiazcpin-2-amine 4-oxide ( chlordiazepoxide ) led to its introduction into clinical use as the active ingredient of the tranquilizer Librium . 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

In contrast to the convulsive-like effects of high doses of PCP compounds, several models of convulsions have been used to demonstrate anticonvulsant properties of PCP in a variety of species. 

This laboratory has utilized two approaches to define further the anticonvulsant properties of PCP. One approach involved a relatively simple convulsant model, pentylenetetrazol-induced convulsions. In this model, the administration of ketamine alone, or in combination with several known anticonvulsants, was tested. Ketamine, as a structural analog of PCP, shares many of the pharmacological properties associated with PCP. The second approach involved a more complex model, hippocampal-kindled seizures. 

The results demonstrate anticonvulsant properties of PCP and ketamine in two quite different seizure models. On the one hand, ketamine was effective in antagonizing several components of PTZ activity. Others have previously reported anti-PTZ effects of ketamine. However, the present results demonstrate that the anticonvulsant effects of ketamine against PTZ seizures closely resembled the effects of phenobarbital in that both compounds delayed clonic convulsions and prevented tonic extension. Moreover, a low dose of ketamine, which alone showed no anticonvulsant effect or overt behavioral changes, potentiated the anti-PTZ effects of phenobarbita 1. These findings suggest that ketamine possesses selective anticonvulsant properties. The anticonvulsant mechanism of action for phenobarbital is not known. However, the similarities between ketamine and phenobarbital, and the interaction between the two compounds, suggest a common mechanism or site of acti on. 

Chen, G., and Bohner, B. Anticonvulsant properties of 1 -(1 -phen-ylcyclohexyl)pi peridine HC1 and certain other drugs. Proc Soc Exp Biol Med 106 632-635. 1961. 

Cannabinoid receptors are expressed throughout the cerebral cortex and the hippocampus, and a subpopulation of these cells appear to show an unusually high level of activity. It is possible that cells in these areas modulate the sensory effects of cannabis, particularly the effects on perception, task performance and memory. In addition, the anticonvulsant properties of cannabis are believed to be mediated here. Parts of the hypothalamus show high levels of receptor sites for cannabinoids this may be related to hypothermia effects. High levels in the cerebellum may be related to mediating the property of cannabinoids that produces the reduction in ataxic (muscle co-ordination) symptoms in certain disorders (Herkenham et al., 1991). 

Valproic acid is the common name for 2-propylpentanoic acid (Epival usually used as its sodium salt), also referred to as n-dipropylacetic acid, is a simple branched-chain carboxylic acid with unique anticonvulsant properties. Valproic acid was first synthesized in 1882 by Burton [75], but there was no known clinical use until its anticonvulsant activity was fortuitously discovered by Pierre Eymard in 1962 in the laboratory of G. Carraz, which was published by Meunier et al. in 1963 [76]. 

Nimodipine may be more effective than verapamil for rapid-cycling bipolar disorder because of its anticonvulsant properties, high lipid solubility, and good penetration into the brain. 

Benzodiazines bind to GABAa receptors, and they have sedative, anxiolytic, muscle relaxant, and anticonvulsant properties. They increase stage 2 sleep and decrease REM and delta sleep. 

Several derivatives of imidazo[2,l-/]theophyllines were synthesized and tested for their CNS activity. Compounds 476 showed significant antiserotonin and long-lasting hypothermic effects, and both 477 and 478 possess anticonvulsant properties <1999EJM1085, 2002FA697>. 

In the United States, anticonvulsant properties have been found in a series of l-methyl-2-phenylcarbamoylpiperidazines [182], The introduction of a methylene bridge into the hexahydro-l,2-diazine system of these compounds has been reported to lead to 2,3-diazabicyclo[2.2.1]heptane congeners with significantly reduced anticonvulsant activity [183]. 

Hiller KO, Zetler G. (1996). Neuropharmacological studies on ethanol extracts of Valeriana officinalis L. behavioural and anticonvulsant properties. Phytother Res. 10(2) 145-151. 

Meier B. (1995). Passiflora incarnata L.—Passion flower. Zeitschrift fur Phytotherapie. 16(2) 115-26. Medina JH, Paladini AC, Wolfman C, Levi de Stein M, Calvo D, Diaz LE, Pena C. (1990). Chrysin (5,7-di-OH-flavone), a naturally-occurring ligand for benzodiazepine receptors, with anticonvulsant properties. Biochem Pharmacol. 40(10) 2227-31. 

The anticonvulsant properties of the drug would appear to be due to its ability to inhibit fast sodium channels, which may be unrelated to its psychotropic effects. Like lithium, it has been shown to decrease the release of noradrenaline and reduce noradrenaline-induced adenylate cyclase activity unlike lithium, it seems to have little effect on tryptophan or 5-HT levels in patients at therapeutically relevant concentrations. It also reduces dopamine turnover in manic patients and increases acetylcholine... 

Primidone is chemically and structurally similar to phenobarbital with the exception that the carbonyl group on Cj is replaced by a methylene group. This modification leads to the production of a drug with strong anticonvulsant properties without expressed soporific effects. 

Buspirone is as effective as the benzodiazepines in the treatment of general anxiety. However, the full anxiolytic effect of buspirone takes several weeks to develop, whereas the anxiolytic effect of the benzodiazepines is maximal after a few days of therapy. In therapeutic doses, buspirone has little or no sedative effect and lacks the muscle relaxant and anticonvulsant properties of the benzodiazepines. In addition, buspirone does not potentiate the central nervous system depression caused by sedative-hypnotic drugs or by alcohol, and it does not prevent the symptoms associated with benzodiazepine withdrawal. 

The benzodiazepines constitute the most commonly used group of anxiolytics and sedative-hypnotics. Since the first member of this group, chlordiazepoxide, was introduced, many congeners have been marketed. Most of these drugs possess anxiolytic, sedative-hypnotic, and anticonvulsant properties. Thus, the clinical indications for specific benzodiazepines are not absolute, and their uses overlaps considerably. 

ECT itself has long been recognized to possess anticonvulsant properties, which have been hypothesized to underlie its antidepressant and antimanic effects (Mukherjee 1989 Post et al. 1986c Sackeim et al. 1983). This... 

Neuroimaging techniques assessing cerebral blood flow (CBF] and cerebral metabolic rate provide powerful windows onto the effects of ECT. Nobler et al. [1994] assessed cortical CBE using the planar xenon-133 inhalation technique in 54 patients. The patients were studied just before and 50 minutes after the sixth ECT treatment. At this acute time point, unilateral ECT led to postictal reductions of CBF in the stimulated hemisphere, whereas bilateral ECT led to symmetric anterior frontal CBE reductions. Regardless of electrode placement and stimulus intensity, patients who went on to respond to a course of ECT manifested anterior frontal CBE reductions in this acute postictal period, whereas nonresponders failed to show CBF reductions. Such frontal CBF reductions may reflect functional neural inhibition and may index anticonvulsant properties of ECT. A predictive discriminant function analysis revealed that the CBF changes were sufficiently robust to correctly classify both responders (68% accuracy] and nonresponders (85% accuracy]. More powerful measures of CBF and/or cerebral metabolic rate, as can be obtained with positron-emission tomography, may provide even more sensitive markers of optimal ECT administration. 

DMHP was also found to have anticonvulsant properties. Studies conducted in mice showed that it was 8 times as potent as THC.27... 

Benzodiazepines are highly effective anxiolytics and sedatives. They also have muscle relaxant, amnestic, and anticonvulsant properties. Benzodiazepines effectively treat both acute and chronic generalized anxiety and panic disorder. The high-potency benzodiazepines alprazolam and clonazepam have received more attention as antipanic agents, but double-blind studies also have confirmed the efficacy of diazepam and lorazepam in the treatment of panic disorder. Although only a few benzodiazepines are specifically approved by the... 

Zolpidem and zaleplon are hypnotics that act at the omega-1 receptor of the central GABA receptor complex. This selectivity is hypothesized to be associated with a lower risk of dependence. Unlike benzodiazepines, zolpidem and zaleplon do not appear to have significant anxiolytic, muscle relaxant, or anticonvulsant properties. However, amnestic effects may occur. 

Eymard s khellin derivatives were dissolved in valproic acid and, following the practice of submitting all such compounds for evaluation in an antiepileptic screening model, they were studied for anticonvulsant activity. These preliminary studies revealed profound anticonvulsant activity. Shortly after this, Meunier serendipitously decided to use valproic acid as a solvent for an unrelated coumarin compound and, although chemically dissimilar to Eymard s khellins, this coumarin exhibited identical anticonvulsant properties. The fact that both compounds had been dissolved in the same solvent was realized immediately. The antiepileptic action of valproic acid was thus discovered completely by accident, with the first successful clinical trial occurring in 1963. 

Other agents with anticonvulsant properties that may be of use m the treatment of bipolar disorder include topiramate, gabapentin, tiagabine and carbamazepine (Janicak et al., 2001). 

Solanine hydrochloride has been used as a commercial pesticide. It has sedative and anticonvulsant properties, and has sometimes been used for the treatment of asthma, as well as for cough and common cold. However, gastrointestinal and neurological disorders result from solanine poisoning. Symptoms include nausea, diarrhoea, vomiting, stomach cramps, burning of the throat, headaches and dizziness. Other adverse reactions, in more severe cases, include hallucinations, loss of sensation, paralysis, fever, jaundice, dilated pupils and hypothermia. Solanine overdose can be fatal. 

Onset of anaesthesia is as rapid though not as smooth as after thiopentone administration, but recovery is more rapid with methohexitone and occurs within 2-5 minutes through redistribution. Drowsiness persists for much longer as the drug is slowly metabolised in the liver. While methohexitone has been reported to cause occasional EEG seizure-like activity in epileptics the drug also possesses anticonvulsant properties. 

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