"Non-antiepileptic" drugs have a strong potential as adjuvants in multidrug-resistant epilepsy treatment. In previous study the influence of low doses of digoxin, which do not affect the myocardium, on the anticonvulsant potential of classical commonly used anti-epileptic drugs under conditions of seizures, induced by pentylenetetrazole and maximal electroshock, has been investigated. The aim of the study was to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant potential of carbamazepine and lamotrigine in experimental seizures with different neurochemical mechanisms. Material and methods: A total of 192 random-bred male albino mice weighting 22–25 g were used. Carbamazepine and lamotrigine were administered intragastrically in conditionally effective (ED50) and sub-effective (½ ED50) doses: carbamazepine at doses of 100 and 50 mg/kg; lamotrigine at doses of 25 and 12.5 mg/kg. Digoxin was administered subcutaneously at a sub-cardiotonic dose of 0.8 mg/kg as an adjuvant to carbamazepine and lamotrigine in ½ ED50. Picrotoxin (2.5 mg/kg subcutaneously); thiosemicarbazide (25 mg/kg intraperitoneally); strychnine (1.2 mg/kg subcutaneously); camphor (1000 mg/kg intraperitoneally) were used as convulsant agents. Results: It was found that digoxin not only has its own permanent anticonvulsant effect on different models of paroxysms with different neurochemical mechanisms of development, but also significantly enhances the anticonvulsant potential of carbamazepine (to a lesser extent – lamotrigine) regardless of the pathogenesis of experimental paroxysms. Conclusion: Based on the results, it can be concluded that digoxin has a high potential as an adjuvant medicine in complex epilepsy treatment because it enhances the efficiency of low-dose traditional anticonvulsants carbamazepine and lamotrigine

Відомо, що поряд з основними стрес-адаптивними системами організму одне з вирішальних місць посідає біологічно активний пептид-нейропептид Y (NPY). NPY-біологічно активна сполука пептидної природи, здатна активувати 4 різних підтипи NPY-рецепторів у ссавців. Широка розповсюдженість NPY-рецепторів обумовлює те, що система NPY і NPY-рецепторів бере участь у регулюванні багатьох фізіологічних функцій, серед яких відчуття насичення та голоду, циркадні ритми, реакція організму на стрес, навчання, регуляція судинного тонусу, сну, сексуальної поведінки тощо. Мета. Дослідження впливу низькомолекулярного аналога нейропептиду Y на поведінкову реакцію щурів у тестах «відкрите поле» та «піднесений хрестоподібний лабіринт». Матеріали та методи. Об'єктом дослідження був модифікований кінцевий фрагмент NPY, що містить 9 амінокислотних залишків. Дослідні тварини отримували інтраназально розчин досліджуваного пептиду у дозуванні 0,02 мг/кг, 0,05 мг/кг та 0,1 мг/кг. Фармакологічне вивчення впливу сполуки на поведінкові реакції щурів проводилося в тестах «відкрите поле» та «піднесений хрестоподібний лабіринт». Результати. Експерименти на щурах показали наявність анксіолітичних властивостей у сполуки без супутнього седативного ефекту. В тестах «відкрите поле» і «піднесений хрестоподібний лабіринт» спостерігався активуючий вплив сполуки на локомоторну активність та зниження вегетативних проявів. Висновки. Дані експерименту вказують на те, що модифікований фрагмент нейропептиду Y здатен впливати на рівень тривожності та дослідницької активності щурів, що обґрунтовує доцільність подальшого дослідження цієї експериментальної сполуки. Ключові слова: нейропептид Y; стрес; відкрите поле; піднесений хрестоподібний лабіринт; поведінкові розлади

On the way to the search for effective adjuvant medicines for epilepsy treatment, antidiabetic medicines such as sodium-glucose cotransporter-2 inhibitors, which are expressed not only in the kidneys but also in the brain, attract attention. From previous studies, it is known that dapagliflozin improves electroencephalographic parameters in rats on the model of pentylenetetrazole-induced seizures. However, the anticonvulsant potential of other medicines from this group needs to be clarified. The aim of the study is to estimate the effect of empagliflozin, dapagliflozin per se and their combinations with sodium valproate on pentylenetetrazole-induced seizures, as well as on muscle tone and motor coordination in mice. Material and methods. 42 random-bred male albino mice weighing 24-28 g were used in the experiments. Empagliflozin (20 mg/kg) and dapagliflozin (50 mg/kg) were administered intragastrically for 3 days. The classic anticonvulsant sodium valproate (150 mg/kg) per se, in combination with the medicines mentioned above, was administered in a similar regimen. On the second day, 30 minutes after administering all medicines, their effect on muscle tone and coordination of movements was determined in the rotarod test. On the third day, 30 minutes after the last administration of the medicines, their effect on pentylenetetrazole-induced (80 mg/kg subcutaneously) seizures was studied. Results. For the first time, a pronounced anticonvulsant effect of empagliflozin was established both when used alone (a significant increase in latency of the convulsions and a decrease in lethality by 43 %) and especially in combination with sodium valproate (a significant increase in latency of the convulsions, a decrease in the number and severity of seizures and a decrease in lethality by 83 %), as well as the absence of a muscle relaxant effect in both cases. Dapagliflozin has neither its anticonvulsant properties nor its effect on the action of sodium valproate. However, this medicine caused muscle relaxation, especially when combined with sodium valproate. Conclusions. The results suggest that empagliflozin, unlike dapagliflozin, has a high potential as an adjuvant medicine in treating epilepsy, as it enhances the efficacy of the classic anticonvulsant sodium valproate without muscle relaxant side effects

Neuropeptide Y (NPY) is a biologically active neuropeptide that is responsible for a large list of physiological processes. We propose a short modified fragment of NPY that should at least partially have a spectrum of biological activity of the original peptide. The compound was named nonapeptide NP9. The aim of our study was to investigate the ability of the modified fragment of NPY to influence spatial memory and learning. Materials and methods: the study was performed on 24 one-year-old random-bred female rats weight 220–250 g. The animals were divided into 3 groups of 8 rats each: treated with a solvent (0.9 % NaCl), a solution of peptide NP9 0.02 mg/kg and the drug “Semax” 0.1 mg/kg. All drugs were administered intranasally. The study of the effect of the peptide NP9 on spatial memory and learning ability was performed in the psychopharmacological test the Morris water maze. Navigation parameters were analyzed using Noldus EthoVision XT 14 video tracking software. The escape latency, the distance moved, the average velocity and the meander were recorded. An inter-quadrant analysis of rat behavior was also performed, for which the frequency of appearance and time spent in certain quadrants were recorded. Results: nonapeptide NP9 in the Morris water maze test demonstrated the ability to accelerate the time to find a hidden platform, reduce the distance traveled, meander, and optimize the search strategy. Conclusions: NP9 peptide has demonstrated the ability to positively influence learning and spatial memory. The improvement in cognitive performance of animals administered with the peptide NP9 was no less than that of the reference nootropic drug Semax. These results substantiate the feasibility of further research with the aim of pharmaceutical development of a new nootropic drug

Epilepsy is a chronic neurological disease characterized by a persistent tendency to seizures. The development of new approaches to the treatment of epilepsy is an urgent issue in modern pharmacology. Such studies are especially necessary in view of the growing number of cases of drug-resistant epilepsy, which reaches 30 %. To improve the results of treatment, adjuvant non-antiepileptic drugs are offered. Promising adjuvant agents include, in particular, the lipophilic cardiac glycoside digoxin in subcardiotonic doses as well as non-steroidal anti-inflammatory drugs. Taking into account the important role of neuroinflammation in the pathogenesis of epilepsy, it is necessary to clarify the influence of standard antiepileptic drugs and adjuvant agents on individual links of the inflammatory process and neurons’ damage under the conditions of chronic epileptogenesis. The aim of the work is to determine the effect of digoxin, sodium valproate and celecoxib per se as well as the combination of digoxin with sodium valproate on the content of cyclooxygenase 1 and 2 types (COX-1, COX-2), prostaglandins (PG) E2, F2α, I2, thromboxane (TX) B2, 8-isoprostane and neuron-specific enolase (NSE) in the brain of mice in the pentylenetetrazole (PTZ)-induced kindling model. It was found that during 16 days of kindling (PTZ 30 mg/kg daily) sodium valproate in a sub-effective dose of 150 mg/kg and digoxin 0.8 mg/kg (1/10 LD50) per se moderately effectively affected the course of the seizure syndrome in mice. Sodium valproate significantly (p<0.05) increased the seizure latency and decreased the number of days with convulsions, when digoxin significantly (p<0.05) decreased the number of animals with seizures. Digoxin clearly potentiated the effect of sodium valproate – against the background of their combination, seizures were absent. Celecoxib 4 mg/kg only tended to reduce the number of animals with convulsions. In the brains of untreated animals with the PTZ-kindling model, a clear shift of the cyclooxygenase pathway of the arachidonic acid cascade was revealed, indicating neuroinflammation: the level of COX-1 and especially COX-2, PGF2α, and TXB2 increased, while the content of PGE2 and PGI2 decreased compared to the vehicle control group (p<0.001). These violations occurred against the background of strong oxidative stress, as evidenced by an almost 18-fold increase in the content of cerebral 8-isoprostane (p<0.001), and were accompanied by massive destruction of neurons, the marker of which is a 2.7-fold increase in the content of NSE (p<0.001). The anti-inflammatory and antioxidant properties of digoxin, sodium valproate and especially their combinations have been shown. They are manifested in a significant decrease in the level of COX-1 and COX-2 (p<0.001), an increase in the content of PGE2 and PGI2 (p<0.001), a decrease in the level of PGF2α and TXB2, 8-isoprostane and NSE (p<0.001) compared to the positive control (PC). Despite its selectivity for COX-2, celecoxib had almost no effect on the level of this cerebral COX isoform, mainly inhibiting COX-1. Compared with PC, celecoxib did not have a significant effect on COX-2, PGI2, and NSE, significantly inferior to valproate (except for the effect on PGF2α), digoxin and its combination (except for the effect on COX-1), which corresponds to the absence of a pronounced impact on the course of kindling and indicates the limitation of its anti-inflammatory and antioxidant properties in the CNS without a neurocytoprotective effect. Predominant suppression of COX-2 indicates a moderate selectivity of the combination of valproate and digoxin to this enzyme, which is a predictor of a reduction in the risk of side effects against the background of long-term use. Complete normalization of the level of 8-isoprostane under the combination of valproate + digoxin indicates the most favorable effect on the course of cerebral oxidative stress, as well as the maximum decrease in the content of NSE (p<0.001) indicates the neurocytoprotective properties of this combination in the model of chronic epileptogenesis. The set of obtained results experimentally substantiates the expediency of using a combination of digoxin with classical anticonvulsants, in particular with sodium valproate, to increase the effectiveness of pharmacotherapy of epilepsy.