Antiepileptic activity

The three-point pharmacophore models are shown in Fig. 7. The structures of the y0-alanine analogues and their antiepileptic activities against pilocarpine test are tabulated in Table 3. 

O. A. Salach, S. Hadad, A. Haj-Yehia, S. Sussan, M. Bialer, Comparative Pharmacokinetic and Pharmacodynamic Analysis of Phthaloyl Glycine Derivatives with Potential Antiepileptic Activity , Pharm. Res. 1994, 11, 1429-1434. 

F. Mergen, D. M. Lambert, J. C. Goncalves Saraiva, J. H. Poupaert, P. Dumont, Antiepileptic Activity of l,3-Dihexadecanoylamino-2-valproyl-propan-2-ol, a Prodrug of Valproic Acid Endowed with a Tropism for the Central Nervous System ,. /. Pharm. 

The efficacy of barbiturates as antiepileptic drugs can be attributed to their effect on the stimulation of epileptogenic neurons, and also on the GABA-ergic channel in the CNS by elevating of the inhibitory action of GABA. Furthermore, barbiturates can reduce the excitatory effects of glutamate at synapses. It is not presently known which of these proposed mechanisms is more important for the development of antiepileptic activity. 

Valproic acid, valproate sodium, and (DVP) are carboxylic acid-derivative anticonvulsants. Divalproex sodium is a stable coordination compound consisting of valproic acid and valproate sodium in a 1 1 molar ratio (AHFS, 2000). It is a pro-drug of valproate, dissociating into valproate in the GI tract (AHFS, 2000), and a simple branched-chain carboxylic acid (w-dipropylacetic acid) with antiepileptic activity against a variety of types of seizures (Beydoun et al., 1997). Divalproex sodium has been approved for treating adults with simple and complex absence seizures (Mattson et al., 1992), and for mania. It has shown efficacy across a broad spectrum of BD subtypes (i.e., pure mania, mixed mania, and rapid cycling) (Pope et al., 1991 Bowden et al., 1994). 

Its antiepileptic activity results from its binding to one or more specific GABA receptors increasing GABA mediated inhibition. 

Lorazepam is less lipophilic than diazepam and there is evidence that it has a longer duration of anticonvulsant action than diazepam after intravenous administration. This could be due to the fact that diazepam is more rapidly removed from the brain compartment than lorazepam, which limits its duration of antiepileptic activity. In practice, when diazepam is used to control status epilepticus it is often necessary to continue treatment with diphenylhydantoin, which has a longer duration of action in the brain. The principal hazards of benzodiazepines when given intravenously include respiratory depression and hypotension. Diazepam may be administered rectally, its ease of absorption leading to peak plasma levels within about 10 minutes. 

Actions Phenobarbital (see p. 94) has antiepileptic activity, limiting the spread of seizure discharges in the brain and elevating the seizure threshold. Its mechanism of action is unknown but may involve potentiation of the inhibitory effects of y-aminobutyric acid (GABA)-mediated neurons. Doses required for antiepileptic action are lower than those that cause pronounced CNS depression. 

Peak serum blood concentration of topiramate is achieved 2 to 3 hours after dosing. Peak concentrations in the range of 9.0 to 12 Ug/mL indicate that the dose is appropriate to achieve optimal antiepileptic activity. The minimum blood concentration, achieved just before the next dose, should be >2,0 pg/mL to ensure adequate antiepileptic protection. Concentrations <2.0pg/mL indicate that the dose is either suboptimal or administered too infrequently. Topiramate may be quantified by immunoassay or GLC-FID. 

Benzodiazepines, mephobarbital, and succinimides have antiepileptic activity. However, they are infrequently prescribed for this purpose. 

In summary, THC-like cannabinoids exhibit antiepileptic activity in several animal models. The SAR observed differ considerably from those noted for cannabimimetic or analgetic activity in these series. The unnatural (+ )-(3S,4S)-THCs exhibit either very low, or no activity in MES or AGS tests. 

CBD-like cannabinoids also exhibit antiepileptic activity in several animal models, in contrast to lack of activity in cannabimimetic or analgetic models, in which these compounds are inactive. Surprisingly, the unnatural (+ )-CBD s are at least as active as the (- )-enantiomers in all the animal models for antiepileptic activity in which they have been tested. 

Preclinical data suggest that CBD would be effective for partial seizures and generalized grand mal seizures, but not for petit mal, where it may even reduce the efficacy of currently used antiepileptic drugs. In patients, antiepileptic activity is observed with CBD at high doses. Hence, future research should aim at obtaining more active compounds with a CBD profile of activity. 

Phenobarbital has a broad spectrum of antiepileptic activity and efficacy. It is often used by itself or in combination with phenytoin. Advantages of phenobarbital are ... 

Vglu = Anticonvulsant activity against seizures produced by intraventricular injection of L-glutamate in animals +E = Antiepileptic activity in epileptic palients... 

Off-label use has demonstrated that LTG has broad-spectrum antiepileptic activity. In addition, LTG is used for the treatment of bipolar disease and pain syndromes. 

Subsequent studies in rats found that SRC reduces the plasma levels of phenytoin by about half These pharmacokinetic effects were only seen after multiple doses, not single doses of phenytoin. A pharmacodynamic interaction, resulting in reduced antiepileptic activity was also noted. 

Not understood. There is evidence from animal studies that SRC may affect the pharmacokinetics of the phenytoin and possibly its pharmacodynamics as well, thereby reducing its antiepileptic activity. It is also suggested that one of the ingredients oiSRC may have some antiepileptic activity. ... 

Information about this interaction appears to be limited to these reports. Shankhapushpi (SRC) is given because it has some antiepileptic activity (demonstrated in animal studies ), but there is little point in combining it with phenytoin if the outcome is a fall in plasma phenytoin levels, accompanied by an increase in seizure frequency. For this reason concurrent use should be avoided. SRC is a syrup prepared from Convolvuluspluricaulis leaves, Nardostachysjatamansi rhizomes, Onosma bracteatum leaves and flowers and the whole plant of Centella asiatica, Nepeta hindostana and Nepeta elliptica The first two of these plants appear to contain compounds with antiepileptic activity. ... 

Lappaconitine has been shown to possess antiepileptic activity on rat hippocampal slices [56]. 

Antidiarrheal activity, 1408 Antidiarrheic, 2000 Anti-DNA Topoisomerase II, 2422 Anti-doping tests, 287 Antidote, 63 Antiepilepsirine, 1352 Antiepileptic activity, 1515 Antiestrogenic, 2408 action, 2400 effects, 2412 Antifeedant, 3488 Antifeedant effect, 4091 Antifertility agents, 2388, 2417 Antiflogistic, 2906... 

Sagratella S (1998) Characterization of the in vitro antiepileptic activity of new and old anticonvulsant drugs. Gen Pharmacol 30 153-160 Salter MW (2001) LTP gets culture. Trends Neurosci 24 560-561... 

Fig. 2.7 Some quinoxaline motifs with antiepileptic activity...

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