The aim of this study was to characterize the interaction between 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ-an endogenous parkinsonism-preventing substance) and various antiepileptic drugs [AEDs: clonazepam (CZP), ethosuximide (ETS), gabapentin (GBP), levetiracetam (LEV), tiagabine (TGB) and vigabatrin (VGB)] in the mouse maximal electroshock (MES)-induced seizure model. Results indicate that 1-MeTHIQ in combination with CZP (at the fixed ratios of 50:1 and 25:1), ETS (1:10) and GBP (1:1, 1:2, 1:5 and 1:10) exerted supra-additive (synergistic) interactions in the mouse MES model. In contrast, 1-MeTHIQ in combination with CZP (200:1 and 100:1), ETS (1:1, 1:2 and 1:5), LEV and VGB (1:1, 1:2, 1:5 and 1:10), and TGB (200:1, 100:1, 50:1 and 25:1) produced additive interaction in the mouse MES model. Total brain AED concentrations were unaffected by 1-MeTHIQ, and inversely, CZP, ETS and GBP had no impact on total brain concentrations of 1-MeTHIQ, indicating pharmacodynamic nature of synergistic interactions between 1-MeTHIQ and the tested AEDs in the mouse MES model. In conclusion, the supra-additive interactions of 1-MeTHIQ with CZP (at the fixed ratios of 50:1 and 25:1), ETS (1:10) and GBP (1:1, 1:2, 1:5 and 1:10) in the mouse MES model appear to be particularly favorable combinations from a clinical viewpoint. The additive combinations of 1-MeTHIQ with CZP (100:1, 50:1), ETS (1:1, 1:2 and 1:5), LEV and VGB (1:1, 1:2, 1:5, and 1:10), and TGB (200:1, 100:1, 50:1 and 25:1) seem to be neutral and worthy of consideration in further clinical practice.

Clavulanic acid (CLAV) inhibits bacterial β-lactamases and is commonly used to aid antibiotic therapy. Prompted by the initial evidence suggestive of the potential anticonvulsant and neuroprotective properties of CLAV, the present study was undertaken to systematically evaluate its acute effects on seizure thresholds in seizure tests typically used in primary screening of potential antiepileptic drugs (AEDs). In the present study, 6-Hz seizure threshold, maximal electroshock seizure threshold (MEST) test, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests were used to determine anticonvulsant effects of intraperitoneally (i.p.) administered CLAV in mice. Acute effects on motor coordination and muscle strength were assessed in the chimney and grip-strength tests, respectively. Doses of CLAV studied in the present study were either comparable or extended the doses reported in the literature to be effective against kainic acid-induced convulsions in mice or behaviorally active in rodents and monkeys. CLAV had no effect on seizure thresholds in the 6-Hz (64 ng/kg to 1 mg/kg) and MEST (64 ng/kg to 5 mg/kg) seizure tests. Similarly, CLAV had no effect on seizure thresholds for i.v. PTZ-induced myoclonic twitch, clonic convulsions, and tonic convulsions (64 ng/kg to 5 mg/kg). Finally, CLAV (64 ng/kg to 5 mg/kg) had no effect on the motor performance and muscle strength in the chimney and grip-strength tests, respectively. In summary, CLAV failed to affect seizure thresholds in three seizure tests in mice. Although the results of the present study do not support further development of CLAV as an AED, its beneficial effects in chronic epilepsy models warrant further evaluation owing to its, for example, potential neuroprotective properties.

α-Spinasterol is a plant-derived compound which was reported to act as a selective antagonist for the transient receptor potential vanilloid 1 (TRPV1) receptor. Several studies revealed that the TRPV1 receptors might modulate seizure activity in animal models of seizures and epilepsy. The aim of the present study was to investigate the effect of α-spinasterol on the seizure threshold in three acute models of seizures, i.e., in the intravenous (i.v.) pentylenetetrazole (PTZ) seizure test, in the maximal electroshock seizure threshold (MEST) test and in the model of psychomotor seizures induced by 6 Hz stimulation in mice. Our results revealed significant anticonvulsant effect of α-spinasterol in all the used seizure tests. In the i.v. PTZ test, statistically significant elevation was noted in case of the threshold for myoclonic twitches (doses of 0.1-1 mg/kg) and generalized clonus seizures (doses of 0.5 and 1 mg/kg) but not for tonic seizures. The studied TRPV1 antagonist also increased the threshold for tonic hindlimb extension in the MEST (doses of 0.5 and 1 mg/kg) and 6 Hz psychomotor seizure (doses of 0.1 and 0.5 mg/kg) tests in mice. Furthermore, α-spinasterol did not produce any significant impairment of motor coordination (assessed in the chimney test) and muscular strength (investigated in the grip-strength test) and it did not provoke significant changes in body temperature in mice. Based on the results of our study and the fact that α-spinasterol is characterized by good blood-brain permeability, we postulate further investigation of this compound to precisely evaluate mechanism of its anticonvulsant action and opportunity of its usage in clinical practice.