Anti-seizure activity

As to be expected from a peptide that has been highly conserved during evolution, NPY has many effects, e.g. in the central and peripheral nervous system, in the cardiovascular, metabolic and reproductive system. Central effects include a potent stimulation of food intake and appetite control [2], anxiolytic effects, anti-seizure activity and various forms of neuroendocrine modulation. In the central and peripheral nervous system NPY receptors (mostly Y2 subtype) mediate prejunctional inhibition of neurotransmitter release. In the periphery NPY is a potent direct vasoconstrictor, and it potentiates vasoconstriction by other agents (mostly via Yi receptors) despite reductions of renal blood flow, NPY enhances diuresis and natriuresis. NPY can inhibit pancreatic insulin release and inhibit lipolysis in adipocytes. It also can regulate gut motility and gastrointestinal and renal epithelial secretion. 

Primidone is an other second line barbiturate used orally to control tonic-clonic and partial seizures. It is a pro-drug as it is metabolized to phenobarbital and phenylethylmalonamide (PEMA), however both the parent compound as well as the metabolites have anti seizure activity. Its use is more difficult to monitor and adverse effects occur even more frequently than with phenobarbital. 

Natural Products Investigated for Anti-Seizure Activity... 

Most studies investigated reported anti-seizure activity of a specific non-allopathic preparation using animal models of epilepsy. The usual experimental protocol evaluated the efficacy of a specific substance or preparation in preventing electroshock- versus pentylenetetrazole (PTZ)-induced seizures. 

Q Casimiroa edulis° Extracts used in Mexican traditional medicine as sedative, antihypertensive. Controlled studies demonstrated effective anti-seizure activity comparable to phenobarbital and phenytoin, and eliminated seizure-related mortality in pre-treated animals... 

Introduced initially for absence seizures, this drug is now known to be effective in and used to treat tonic lonic seizures and most types of epilepsy. It was found to inhibit GABA transaminase and so elevate GABA concentrations and inhibition. This is achieved, however, over a slower time-course than its anti-seizure effect, especially experimentally, which is now thought to be due to its phenytoin-like, use-dependent block of sodium channels. Since, unlike phenytoin, the full effect of valproate takes some weeks to develop, its slower effect on GABA metabolism and activity should not be ignored. 

One unwanted side-effect of phenytoin is its anti-folate activity. A programme of synthetic chemistry to manipulate the structure of the anti-folate compound pyri-methium to try to replace that property with anticonvulsant activity resulted in the synthesis of lamotrigine. It proved to be an effective AED in partial and generalised epilepsy but experience has found it also to be of value in absence seizures. 

Parenteral Adjunct in status epilepticus and severe recurrent convulsive seizures. Rectal For selected, refractory patients on stable regimens of anti-epileptic agents who require intermittent use of diazepam to control bouts of increased seizure activity. 

Epilepsy is a neurological disorder characterized by recurrent spontaneous seizures due to an imbalance between cerebral excitability and inhibition, with a tendency towards uncontrolled excitability (Papandreou et al., 2006). Recurrent severe seizures can lead to death of brain cells. Phenytoin (Dilantin, Phenytek) is a widely used anti-seizure medicine (LaRoche, 2007). The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited, possibly by promoting sodium efflux from neurons. Phenytoin tends to stabilize the threshold against hyper-excitability caused by excessive stimulation. The current status of new (second generation) anti-epileptic drugs has been recently reviewed (Bialer et al., 2007). 

Riluzol antagonizes glutamatergic transmission via different mechanisms indirect blockade of NMDA receptors (modification of receptor phosphorylation status), inhibition of excitatory amino acid release by an agonist effect on an unknown receptor bound to protein G or interaction with voltage-dependent sodium channels (depressor effect on neurones with a high tonic activity spontaneously). The pharmacological properties of the compound can be explained by these mechanisms anti-seizure, anti-ischaemia, antagonism of MPTP cytotoxicity [201]. 

Sabeluzol is a substance which stimulates learning processes and recall, has an anti-hypoxic and anti-seizure effect. The two enantiomers contribute to the pharmacological activity. This compound increases long-term potentiation at 2,5 mg/kg in the rat and counteracts chronic glutamate toxicity in... 

A heat-treated commercial milk formula became popular for breastfeeding infants in the US in the 1950s. However, it was discovered that the formula was deficient in vitamin Bg and also had some anti-pyridoxine activity. Some of the babies fed on this formula became ill with epileptic symptoms, similar to PDS. Seizures and electroencephalogram (EEG) abnormalities vanished within a few minutes after pyridoxine injection. 

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. 

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