Maximal electroshock seizure

A series of 1-substituted 3-phenylbenzazepines have been evaluated. It was found that the aminopropyl derivative (6, n = 3 R1 = R2 = Et) counteracted amphetamine toxicity, and that the piperazinyl derivative (6) (n = 2 NR R2 = N(CH2CH2)2 = NCH2CH2OH) gave protection against maximal electroshock seizures (MES) [12]. None of the other derivatives such as the 2-oxo derivatives showed any significant effects on the central nervous or cardiovascular system, nor did any of them exhibit any diuretic or hypo-glycaemic activity [12]. Several similar compounds possess antiarrhythmic and antihypertensive effects this will be mentioned in a later section. 

The mechanism of action of carbamazepine appears to be similar to that of phenytoin. Like phenytoin, carbamazepine shows activity against maximal electroshock seizures. Carbamazepine, like phenytoin, blocks sodium channels at therapeutic concentrations and inhibits high-frequency repetitive firing in neurons in culture (Figure 24-4). It also acts presynaptically to decrease synaptic transmission. These effects probably account for the anticonvulsant action of carbamazepine. Binding studies show that carbamazepine interacts with adenosine receptors, but the functional significance of this observation is not known. 

Phensuximide and methsuximide are phenylsuccinimides that were developed and marketed before ethosuximide. They are used primarily as antiabsence drugs. Methsuximide is generally considered more toxic, and phensuximide less effective, than ethosuximide. Unlike ethosuximide, these two compounds have some activity against maximal electroshock seizures, and methsuximide has been used for partial seizures by some investigators. 

In cell culture preparations, diphenylhydantoin, carbamazepine and valproate have been shown to reduce membrane excitability at therapeutically relevant concentrations. This membrane-stabilizing effect is probably due to a block in the sodium channels. High concentrations of diazepam also have similar effects, and the membrane-stabilizing action correlates with the action of these anticonvulsants in inhibiting maximal electroshock seizures. Intracellular studies have shown that, in synaptosomes, most anticonvulsants inhibit calcium-dependent calmodulin protein kinase, an effect which would contribute to a reduction in neurotransmitter release. This action of anticonvulsants would appear to correlate with the potency of the drugs in inhibiting electroshock seizures. The result of all these disparate actions of anticonvulsants would be to diminish synaptic efficacy and thereby reduce seizure spread from an epileptic focus. 

The carbohydrate-based 1,3,2-dioxathiolane A, -dioxide 23 (Section 6.05.3.1) has demonstrated an exceptional anticonvulsant activity in the standard maximal electroshock seizure test. Compound 23 is much more potent than structural analogs, and approximately 8 times more potent than the isosteric topiramate <1998JME1315>. 

The maximal electroshock seizure (MES) test was used to show efficacy of antiepileptic agents against partial and generalized seizure type epilepsy among therapy-resistant epileptic patients. 

Aminoethers such as 32 protected against maximal electroshock seizures in rats.79... 

A ter el at. (1984) documented the anticonvulsant properties of PBO and compared them with those of clinically established anti epileptic drugs. PBO administered inlrapcritoncally to mice exerted peak anti maximal electroshock activity and peak neurotoxicity at 5 and 7 hours, respectively. The median neuroluxic dose was I.69U mg kg"1. In the maximal electroshock seizure test I he median effective dose (HD j) was 457 mg kg"1 and the protective index (PI) was 3,69. In the subcutaneous pentylenetetrazol (PTZ) test the ED u was 443 mg kg 1 and PI was 3.81. PBO prevented seizure spread and elevated seizure threshold, and its PI compared favourably with those of clinically useful anticonvulsants,... 

Meyer (1979) reported that the activity of yangonin and desmethoxyyan-gonin (administered intraperitoneally, ip) in preventing mice from maximal electroshock seizure was markedly increased when given in combination with the other kava constituents. 

The following abbreviations are used in the present review THC (tetrahydrocannabinol) CBD (cannabidiol) CBN (cannabinol) DMH (1,1-dimethylheptyl) SAR (structure-activity relationship) cisplatin (m-diam-minedichloroplatinum(II)) GABA (y-aminobutyric acid) MES (maximal electroshock seizures) PTZ (pentylenetetrazol) AGS (audiogenic seizure) IOP (intraocular pressure). 

Fox, D. A., Overmann, S. R. and Woolley, D. E. (1979b). Neurobehavioral ontogeny of neonatally lead-exposed rats. II. Maximal electroshock seizures in developing and adult rats. Neurotoxicology, 1, 149... 

Finally, various compounds related to methaqualone have been found to possess anticonvulsant activity in mice . Compound XXXI was found to be more active than methaqualone against maximal electroshock seizures. Compound XXXII also possessed potent anticonvulsant activity but was more toxic than Compound XXXI. 

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