A once-per-day, drug-in-food protocol for prolonged administration of antiepileptic drugs in animal models.

PURPOSE: Convenient and effective methods for administering potential antiepileptic drugs (AEDs) chronically should facilitate many experiments in animal models of chronic epilepsy with spontaneous recurrent seizures. This proof-of-principle study aimed to optimize a once-per-day, drug-in-food protocol by testing the effect of carbamazepine (CBZ) on the frequency of convulsive seizures in rats with kainate-induced epilepsy. METHODS: Adult male rats were given repeated low-dose kainate injections until convulsive status epilepticus persisted for >3 h. After the rats developed spontaneous recurrent seizures, food pellets with CBZ (30, 100, or 300 mg/kg/day) were provided once per day in three 2-week trials (n = 7-9 rats) involving 5 days of CBZ or control treatment, separated by two recovery days within a trial. The total amount of food provided and consumed per day corresponded to a normal caloric diet (60 g/kg/day). KEY FINDINGS: When provided once per day, all animals ate the CBZ-containing food irregularly but continuously throughout the 24-h day. With this daily feeding protocol, CBZ significantly reduced the frequency of spontaneous convulsive seizures in a dose-dependent manner. It is important to note that the effect of CBZ was consistent across the 5 days and throughout each day of the trials. With food administered at 9:00 a.m., and blood assayed at 5:00 p.m., higher food levels of CBZ resulted in higher plasma concentrations of CBZ. SIGNIFICANCE: This AED-in-food protocol is simple, efficient, inexpensive, reliable, and noninvasive; it allows easier long-term drug administration and is less stressful and more humane than other methods of AED administration.

Determination of Artemisinin in Bulk and Pharmaceutical Dosage Forms using HPTLC.

A new, simple, rapid, accurate and precise HPTLC method was developed. The detector response was linear for concentrations between 100-600 ng/spot (r =0.9931). The limits of detection and quantitation were 25 ng/spot and 75 ng/spot, respectively. The recovery study was carried out by standard addition method and was found to be 99.60+/-0.27. Statistical analysis proved that the method was precise, accurate and reproducible, and hence was suitable for the routine analysis of artemisinin.

Comparative efficacy of liposome-entrapped amiloride and free amiloride in animal models of seizures and serum potassium in mice.

The present study was aimed to evaluate a liposomal formulation of amiloride on experimental seizure models including the increasing current electroshock seizure threshold test (ICES), pentylenetetrazole (PTZ)-induced seizures and PTZ-induced status epilepticus in mice. Further, the effect of liposomal amiloride on serum K(+) levels was also investigated using flame photometry. We found an improved anticonvulsant action with liposome-entrapped amiloride as compared to free amiloride. Further, free amiloride showed an increase in serum K(+) levels, however the latter was unaffected with liposomal formulation treatment. These results, together with previously published data, suggest that as drug delivery vehicles, liposomes can enhance the effectiveness of drugs in the CNS without producing peripheral toxicity (hyperkalemia).

Effects of gabapentin and antidepressant drug combinations on convulsions and memory in mice.

In epileptic patients, neurobehavioral problems such as cognitive impairment, depression, and psychosocial impairments have been described, which may have a pathological and/or iatrogenic basis. For this reason additional treatment is required, beside antiepileptic drug (AED) therapy, to correct the accompanying neurological deficits. However, the rationale behind use of antidepressants along with antiepileptics has been questioned due to proconvulsant effects of the former. In the present study, the effect of gabapentin (GBP) on seizure score and memory is evaluated when it is given alone and in combination with some antidepressants, such as sertraline (SERTR) and alprazolam (ALP). Pentetrazole (PTZ)-induced convulsion and spontaneous alternation behavior (SAB) models were used to study the anticonvulsant effect and effect on memory, respectively. Results showed that addition of SERT to GBP or ALP resulted in reduction of anticonvulsant efficacy of these drugs. However, the combination of GBP + SERT + ALP was superior as far as effect on seizure severity and memory was concerned.