Myorelaxant Activity Research Articles

Electrophysiology, molecular modelling, and functional analysis of the effects of dietary quercetin and flavonoid analogues on Kir6.1 channels in rat stomach fundus smooth muscle

Flavonoids, ubiquitously distributed in the plant world, are regularly ingested with diets rich in fruit, vegetables, wine, and tea. During digestion, they are partially absorbed in the stomach. The present work aimed to assess the in vitro effects of quercetin and ten structurally related flavonoids on the rat gastric fundus smooth muscle, focussing on ATP-dependent K+ (Kir6.1) channels, which play a central role in the regulation of resting membrane potential, membrane excitability and, consequently, of gastric motility. Whole-cell currents through Kir6.1 channels (IKir6.1) were recorded with the patch-clamp technique and the mechanical activity of gastric fundus smooth muscle strips was studied under isometric conditions. Galangin ≈ tamarixetin > quercetin > kaempferol > isorhamnetin ≈ luteolin ≈ fisetin > (±)-taxifolin inhibited pinacidil-evoked, glibenclamide-sensitive IKir6.1 in a concentration-dependent manner. Morin, rutin, and myricetin were ineffective. The steric hindrance of the molecule and the number and position of hydroxyl groups on the B ring played an important role in the activity of the molecule. Molecular docking simulations revealed a possible binding site for flavonoids in the C-terminal domain of the Kir6.1 channel subunit SUR2B, in a flexible loop formed by residues 251 to 254 of chains C and D. Galangin and tamarixetin, but not rutin relaxed both high K+- and carbachol-induced contraction of fundus strips in a concentration-dependent manner. Furthermore, both flavonoids shifted to the right the concentration-relaxation curves to either pinacidil or L-cysteine constructed in strips pre-contracted by high K+, rutin being ineffective. In conclusion, IKir6.1 inhibition exerted by dietary flavonoids might counterbalance their myorelaxant activity, affect gastric accommodation or, at least, some stages of digestion.

Research Advancements on Fluorinated and Non-Fluorinated 4- Phenyl(thio)ureido-Substituted 2,2-Dimethylchromans Acting as Inhibitors of Insulin Release and Smooth Muscle Relaxants.

The present study aimed at characterizing the impact of the presence or absence of fluorine atoms on the phenyl and benzopyran rings of 4-phenyl(thio)ureido-substituted 2,2- dimethylchromans on their ability to inhibit insulin release from pancreatic β-cells or to relax vascular smooth muscle cells. Most compounds were found to inhibit insulin secretion and to provoke a marked myorelaxant activity. The lack of a fluorine or chlorine atom at the 6-position of the 2,2-dimethylchroman core structure reduced the inhibitory activity on the pancreatic endocrine tissue. One of the most active compounds on both tissues, compound 11h (BPDZ 678), was selected for further pharmacological investigations. The biological data suggested that 11h mainly expressed the profile of a KATP channel opener on pancreatic β-cells, although a calcium entry blockade effect was also observed. On vascular smooth muscle cells, 11h behaved as a calcium entry blocker.

Repositioning of tubocurarine as analgesic and anti-inflammatory agent: Exploring beyond myorelaxant activity

Background and purposeTubocurarine (d-TC), a non-depolarizing competitive blocker of nicotinic acetylcholine receptors is extensively utilized for the relaxation of skeletal muscles. Drug repositioning is a forthright approach to reduce the cost and speed up drug development process. Herein, we have attempted to evaluate the analgesic and anti-inflammatory activity of d-TC for its possible repurposing in pain and inflammation-related issues.Experimental approach.We examined the soluble epoxide hydrolase inhibitory (sEHI) activity of d-TC employing in silico high throughput screening protocols, in vitro cell-free sEH inhibitory assay, and in in vivo rodent models for its repositioning in pain and inflammation-related disorders.Key results.In molecular docking study, d-TC displayed impressive hydrogen bonding interactions within the cavity of sEH enzyme with good docking score. d-TC also exhibited notable sEH inhibitory activity (IC50 3.72 nm) at the in vitro assay. Oral absorption capability of d-TC (0.1 and 0.2 mg/mL) was determined using an in vitro everted intestinal sac model employing rat ileum tissue that revealed significant oral absorption of d-TC. Besides, in vivo studies revealed that oral administration of d-TC (0.1 and 0.2 mg/kg) in rodents significantly attenuated hyperalgesia (cold plate test, tail immersion test and formalin test) and inflammation (estimation of rectal temperature, acetic acid induced pleurisy test and cotton pellet-induced granuloma test) induced in robust preclinical models.Conclusion and implicationsThese findings are novel and warrant immediate efforts to reposition d-TC as a new therapeutic candidate in the management of hyperalgesia, inflammation, and associated conditions.

Vietnamese Dalbergia tonkinensis: A Promising Source of Mono- and Bifunctional Vasodilators.

Hypertension is a risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality in the world. In the search for new molecules capable of targeting KCa1.1 and CaV1.2 channels, the expression of which is altered in hypertension, the in vitro vascular effects of a series of flavonoids extracted from the heartwoods, roots, and leaves of Dalbergia tonkinensis Prain, widely used in traditional medicine, were assessed. Rat aorta rings, tail artery myocytes, and docking and molecular dynamics simulations were used to analyse their effect on these channels. Formononetin, orobol, pinocembrin, and biochanin A showed a marked myorelaxant activity, particularly in rings stimulated by moderate rather than high KCl concentrations. Ba2+ currents through CaV1.2 channels (IBa1.2) were blocked in a concentration-dependent manner by sativanone, 3′-O-methylviolanone, pinocembrin, and biochanin A, while it was stimulated by ambocin. Sativanone, dalsissooside, and eriodictyol inhibited, while tectorigenin 7-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside], ambocin, butin, and biochanin A increased IKCa1.1. In silico analyses showed that biochanin A, sativanone, and pinocembrin bound with high affinity in target-sensing regions of both channels, providing insight into their potential mechanism of action. In conclusion, Dalbergia tonkinensis is a valuable source of mono- and bifunctional, vasoactive scaffolds for the development of novel antihypertensive drugs.

Phytochemistry and Biological Activities of Amburana cearensis (Allemão) ACSm.

Amburana cearensis (Allemão) ACSm. belongs to the Fabaceae family and occurs in the Brazilian semiarid, Argentina, Paraguay, Bolivia, and Peru. Numerous studies that portray its ethnobotany, use in popular medicine, chemical composition, and biological activities exist in the literature. This review aimed to provide an overview of the chemical composition, ethnopharmacology, and biological activities associated with A. cearensis and its isolated constituents. Information was collected from internet searches in the Scopus, Medline, PubMed, Google Scholar, and ScienceDirect databases were performed covering publications from 1997–2020. An ethnopharmacological literature analysis revealed that A. cearensis is used to treat a wide range of respiratory disorders in addition to intestinal, circulatory, and inflammatory problems. Coumarins, flavonoids, phenolic glycosides, phenolic acids, phenylpropanoid derivatives, and triterpenoids, among others, have been reported as active compounds, with High-Performance Liquid Chromatography (HPLC) being the main analytical technique used. The A. cearensis extracts and compounds presented several biological activities, including antimicrobial, antinociceptive, anti-inflammatory, antioxidant, neuroprotective, and myorelaxant activities, among others. This review provides a useful bibliography for future investigations and A. cearensis applications; however, future studies should focus on its toxic effects and the mechanisms of action of its extracts and isolated constituents to guide clinical applications.

Kalanchoe Pinnata aqueous extract has the potential to improve haematological profile and fatigue status of mice subjected to Free Swimming Endurance Test

Introduction: Kalanchoe pinnata extracts have been shown to possess beneficial cardiovascular effects, analgesic and myorelaxant activities. This study aimed at evaluating the haematological and anti-fatigue effects of its aqueous extract. Materials and methods: This was an in vivo pharmacological experiment, carried out in the Laboratory of Zoology, University of Buea, from January to May 2018. A total of 48 mice were subjected to a 90mins/day-free endurance swimming test for 14 days. Two groups of mice received distilled water and 12% NaCl solution, respectively. Five groups received the plant extract (25, 50, 100 and 200 mg/kg/day) and 200mg/kg/day+NaCl. One positive control group received 5% Vitamin C (1.97mg/kg/day). All administrations were by gavage. Maximum swimming time, glycaemia, lactatemia, uremia, triglyceridemia, haematological indices, tissue glutathion peroxidase, malondialdehyde, glucose and creatine kinase-MB in the heart or gastrocnemius muscle were measured. Results: K. pinnata (50 and 100mg/kg/day) induced a non-significant increase of the swimming duration, compared to neutral control. However, the 12%NaCl group recorded a significant (P<0.05) increase. In the blood, NaCl induced a decrease of platelets that was significantly reverted by the extract in the 200mg/kg+NaCl group. The extract prevented the increase of the level of CK-MB in NaCl group and decreased the serum triglycerides, glucose, urea nitrogen and Lactate levels. In the tissues, MDA and CK-MB levels significantly increased (P<0.001) in the negative control. These increases were significantly (P<0.001) prevented by K. pinnata (200mg/kg/day). Conclusions: Significant biochemical variations support the hypothesis that K. pinnata could be used to delay exercise induced fatigue.

Toxicity of methyl eugenol against Drosophila melanogaster and its myorelaxant activity in bronchioles isolated from Sus scrofa domesticus

This study aimed to evaluate the toxic action of methyl eugenol against Drosophila melanogaster and to evaluate the myorelaxant effect of this constituent on bronchioles isolated from swine from the Sus scrofa domesticus species. The toxicity assay was performed using the fumigation method while myorelaxant activity was assessed by the administration of increasing and cumulative concentrations (1–1000 μM) to swine bronchial rings under 1 gF tension in an organ bath precontracted with 60 mM potassium chloride (KCl) and 10 μM acetylcholine (ACh). The results showed that methyl eugenol possessed insecticidal action (LC50 0.116 μg/mL of air). The compound showed a myorelaxant activity over bronchioles (IC50 of 25.50±14.93 μM and 12.79±9.57 μM for KCl and ACh, respectively). This study serves as starting point for further detailed studies focusing on both the insecticidal and bronchodilatory activity of methyl eugenol.

Myorelaxation, respiratory depression and electrocardiographic changes caused by the administration of extract of açai (Euterpe oleracea Mart.) stone in rats.

The biological and pharmacological properties of natural polyphenols of the extract of Euterpe oleracea stone (EEOS) are associated with the central nervous system (CNS). To investigate the sedative and myorelaxant activity of EEOS in vivo, this study aimed to present the myorelaxant and sedative effects of EEOS in Wistar rats using spontaneous locomotor activity and motor electrophysiology. A total of 108 animals were used in the following experiments: a) behavioral tests (n = 27); b) electromyographic recordings of skeletal muscle (n = 27); c) respiratory muscle activity recordings (n = 27); d) cardiac muscle activity recordings (n = 27). The behavioral characteristics were measured according to the latency time of onset, the transient loss of posture reflex and maximum muscle relaxation. Electrodes were implanted in the gastrocnemius muscle and in the tenth intercostal space for electromyographic (EMG) signal capture to record muscle contraction, and in the D2 lead for electrocardiogram acquisition. After using the 300 mg/kg dose of EEOS intraperitoneally, a myorelaxant activity exhibited a lower frequency of contractility with an amplitude pattern of low and short duration at gastrocnemius muscle and intercostal muscle, which clearly describes a myorelaxant activity and changes in cardiac activity. The present report is so far the first study to demonstrate the myorelaxant activity of this extract, indicating an alternative route for açai stone valorization and its application in pharmaceutical fields.

Compounds with myorelaxant activity from the leaves of Mareya micrantha (Benth.) Müll. Arg. (Euphorbiaceae)

Mareya micrantha (Euphorbiaceae) is an Ivorian medicinal plant widely used in gastrointestinal disorders. So as to understand and identify metabolites possibly implicated in the activity of the plant on intestinal muscles, this study has been undertaken. From the crude ethanolic extract EE of the leaves, hexanic (EH), chloromethylene (EC), ethyl acetatic (EA) and butanolic (EB) sub-extracts were prepared as well as the hydroethanolic residual phase dried (Ar) and their effects on the isolated duodenum of rabbits were determined. If the sub-extracts EH, EA and EB, but also Ar, confirmed the myostimulant activity of the crude extract EE, this was not the case of EC which showed myorelaxant activity. This sub-extract, subjected to purification, led to the isolation of three major triterpenoids type 29-norcucurbitacin (1-3) whose structures were confirmed using the combined analyses of their spectroscopic data (UV, MS, 1D NMR and 2D). All these molecules have shown myorelaxant activity, the most significant one being 2 with an IC50 value of 36.9 µM. These molecules would act by blocking both intracellular and extracellular calcium.

Myorelaxant action of the Dysphania ambrosioides (L.) Mosyakin & Clemants essential oil and its major constituent α-terpinene in isolated rat trachea

This study aimed to investigate the myorelaxant action of the Dysphania ambrosioides essential oil (EODa) and its major constituent α-terpinene on tracheal smooth muscle isolated from rats. In tracheal smooth muscle ex vivo, in organ baths, isometric contractions recordings were done in order to evaluated the effect of EODa (1–1000 μg/mL) and α-terpinene (1–3000 μg/mL) on the following parameters: basal tone, contractions evoked by potassium (KCl 60 mM), acetylcholine (ACh 10 μM) or serotonin (5-HT 10 μM). The EODa and its major constituent α-terpinene, did not statistically alter basal tone; however, they induced myorelaxant effects on top of contractions induced by KCl, ACh and 5-HT. EODa and α-terpinene also inhibited the contractions induced by barium in presence of High [K+] (80 mM). The data suggest that the relaxation induced by these agents is caused by the inhibition of L-type VGCC, inhibiting the inward Ca2+ current through these channels, but does not exclude the possibility of participation of other mechanisms. Results from this study also suggest the EODa, due to their efficacy on relaxation of the respiratory tract, posses a therapeutic potential as a antispasmodic agent for respiratory tract.

Seasonal Variation in the Essential Oil Composition of Mentha aquatica L. and its Myorelaxant Activity

The present investigation was accomplished to study the chemical variability of the essential oil of the plant Mentha aquatica L. collected from Bhimtal, Uttarakhand, India during different seasons ranging from April to December. The essential oils collected at various month intervals were subjected to be analyzed with GC along with MS and FID for their comparative chemical composition analysis. Significant differences in the chemical variability were observed in major components of each collection. Linalool represents the dominating compound in every six collections from April to September comprising a total of 30.1 %, 25.2 %, 33.5 %, 48.4 %, 31.1 % and 45.7 % respectively of total oil composition while linalool acetate represents the dominating compound in next three collections from October to December comprising a total of 46.98 %, 42.1 % and 48.0 % respectively of total oil compositions. Thereafter, the essential oil of the tested plant was subjected to assess the efficiency of myorelaxant activity on the isolated duodenum muscles of Swiss Albino mice. Essential oil at different treatments of 2000 μg and 4000 μg resulted into least to the mild grade of relaxation in the muscles evaluated against the maximum response towards acetylcholine, adrenaline, atropine and propanalol.

Antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil in mice

Chronic pain management has several adverse effects and research looking for new and effective pain management drugs posing lower undesirable effects is necessary. Given the above, the pharmacological investigation of medicinal plants significantly contributes to the dissemination of plant-derived therapeutics. The aim of this study was to evaluate the antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil (PBEO) and the participation of the opioid pathway in this effect in mice. Swiss Mus musculus male mice were tested using acute nociception models (acetic acid induced abdominal contortions, formalin, capsaicin and hot plate tests). The possible myorelaxant action of the PBEO was tested using the rotarod test. The essential oil reduced animal nociception in chemical and heat models, with this action being devoid of a myorelaxant effect. Naloxone (2 mg/kg, intraperitoneally – i.p.) partially antagonized the PBEO activity, possibly acting via opioid receptors. The results obtained provide evidence that the traditional Psidium brownianum use may be effective for pain treatment.

Effects of the Hyptis martiusii Benth. leaf essential oil and 1,8-cineole (eucalyptol) on the central nervous system of mice

The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50 100 and 200 mg/kg, i.p.) and its major compound (50 mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.

Neutral/negative α1-AR antagonists and calcium channel blockers at comparison in functional tests on guinea-pig smooth muscle and myocardium

Constitutive (agonist-independent) activity is a prerogative of many G protein-coupled receptors (GPCRs) including α1-adrenoceptors (α1-ARs). Inhibition of such an activity at α1-AR subtypes by antagonists with negative efficacy is difficult to be adequately tested. In the present experimental approach, we compared the activity of three calcium channel blockers (nifedipine, diltiazem and verapamil) and of three potent benzodioxane-based α1-AR antagonists, differing for subtype selectivity and inverse agonist properties, in producing smooth muscle relaxation and negative inotropy under the same test conditions. We selected, as benzodioxane derivatives, (S)-WB4101, inverse agonist with slight α1A/α1B-α1D AR selectivity, and two previously developed analogues. Both of these are potent antagonists at α1D-AR, that is the α1- AR subtype suspected of the highest susceptibility to inverse agonists for its high degree of basal activity, but only one is inverse agonist. We found that all the three benzodioxane-related α1-AR antagonists have significant intrinsic relaxant activity on non-vascular smooth muscle and moderate negative inotropic effect, while they do not relax aorta. Their potency is always lower than that of three calcium channel blockers. Intrinsic myorelaxant and negative inotropic activity of the three benzodioxane-based α1-AR antagonist is related neither to a particular profile of α1-AR subtype selectivity nor to whether or not being an inverse agonist, but it parallels the calcium antagonists effects indicating a direct interaction of the three α1-AR antagonists with L-type Ca2+ channels.

Myorelaxant Activity of essential oil from Origanum majorana L. on rat and rabbit

Ethnopharmacological relevanceOriganum majorana L. (Lamiaceae) was usually used in Moroccan folk medicine to treat infantile colic and abdominal discomfort. Materials and methodsThe essential oil from the aerial part of the dry Origanum majorana L. (EOOM) was obtained through hydro distillation and analyzed by gas chromatography/mass spectrometry (GC/MS). The effect of EOOM on muscle relaxation was measured on rabbit and rat intestinal smooth muscle mounted in an isotonic transducer. Results1) The main compounds obtained from the aqueous extract of this plant were alpha Terpineol, L-terpinen-4-ol and Beta.-Linalool. 2) EOOM inhibited in a concentration-dependent manner spontaneous contraction of rabbit jejunum, with an IC50 = 64.08 ± 2.42 μg/mL. 3) In rat intestine, EOOM induced the relaxation of the tissue in concentration-dependent manner with an IC50 = 39.70 ± 2.29 μg/mL when the tissue was pre-contracted with CCh 10-6 M, and 48.70 ± 2.26 μg/mL when the tissue was pre-contracted with 25 mM KCl. 4) The relaxation effect induced by EOOM was more important than that obtained in the presence of atropine, hexamethonium, Nifedipine, L-NAME and Blue of methylene. Conclusionthe present result indicates that essential oil of Origanum majorana L. exhibit an effect on intestinal relaxation in vitro. This effect further validates the traditional use of Origanum majorana L. to treat infantile colic and abdominal discomfort.

Antispasmodic and Myorelaxant Activity of Organic Fractions from Origanum majorana L. on Intestinal Smooth Muscle of Rodents

Antispasmodic and Myorelaxant Activity of Organic Fractions from Origanum majorana L. on Intestinal Smooth Muscle of Rodents

Essential oil of Croton Zehntneri attenuates lung injury in the OVA-induced asthma model

ABSTRACTObjective: Croton zehntneri Pax et Hoffm. is a Euphorbiaceae species, popularly known as “canela de cunhã,” a native plant of northeastern Brazil, whose essential oil (EOCZ) shows relatively specific myorelaxant action for the smooth muscle of the airways and in the respiratory tract. Based on this information, EOCZ figures as a candidate for testing in the treatment of asthma, and the present study investigated the benefits of using EOCZ in an ovalbumin-induced asthma model. Methods: 48 male BALB/c mice were divided into six groups (n = 8). In the ST, SO100, and SO300 groups, mice were sensitized and challenged with saline, and then treated with 200 µL of 0.1% Tween 80, 100 mg/kg EOCZ and 300 mg/kg EOCZ, respectively. In the OT, OO100, and OO300 groups, mice were sensitized and challenged with OVA, and then treated with 200 µL of 0.1% Tween 80, 100 mg/kg EOCZ and 300 mg/kg EOCZ, respectively. Results: Our results demonstrated significant changes in all respiratory mechanics variables analyzed between the OO300 and OT groups demonstrating the effectiveness of EOCZ to attenuate the OVA-induced lung injury. In addition, the use of EOCZ at a dose of 300 mg/kg showed an antioxidant effect and decreased inflammatory cells in the pulmonary parenchyma. In conclusion, our results demonstrated that EOCZ was able to improve the lesion in the respiratory system of mice subjected to OVA-induced asthma. Conclusions: The antioxidant action of EOCZ was likely the main mechanism of action in the reversal of this lesion, so more tests should be performed for its confirmation.

Deciphering Structure-Activity Relationships in a Series of 2,2-Dimethylchromans Acting as Inhibitors of Insulin Release and Smooth Muscle Relaxants.

4,6-Disubstituted 2,2-dimethylchromans are reported as pharmacologically active compounds that mainly target the ATP-sensitive potassium channels. The present study is an attempt to characterize the impact of the nature of substituents introduced at the 4- and 6-positions of 2,2-dimethylchromans on their capacities to inhibit insulin release from pancreatic β-cells or to relax vascular smooth muscle cells, both biological responses that are supposed to reflect interaction with specific ion channels. From the core structure 4-amino-2,2-dimethylchroman, a progressive increase in the steric hindrance of the chemical functionalities introduced at the 4-position (amino, formamido, acetamido, arylureido/thioureido) and at the 6-position (amino, formamido, acetamido, alkoxycarbonylamino) led to a progressive magnification of the inhibitory effect on the insulin release process and, to a lesser extent, of the vasorelaxant activity. Moreover, the dextrorotatory enantiomer of 2,2-dimethylchroman compound 29 was more potent than its levorotatory counterpart for inhibiting the insulin secretory process. Additional pharmacological investigations suggested, however, that the myorelaxant activity of 11 and 15 resulted from a direct Ca2+ entry blockade.

Field Based 3D-QSAR Model of KATP Channel Activation by 4, 6 Di-substituted Benzopyran Derivatives

Background: A 3D-QSAR model of KATP channel activation by benzopyran derivatives has been developed using molecular field alignment method. The model based on pED50 values required for myorelaxant activity by 4, 6 disubstituted benzopyrans has been explored. Keywords: KATP channel activation, field based 3D-QSAR, 4, 6 di-substituted benzopyran derivatives.

ПСИХОТРОПНІ ВЛАСТИВОСТІ ПОТЕНЦІЙНОГО АНТИКОНВУЛЬСАНТА 1-(4-МЕТОКСИФЕНІЛ)-5-{2-[4-(4-МЕТОКСИФЕНІЛ)ПІПЕРАЗИН-1-ІЛ]-2-ОКСОЕТИЛ}- 1,5-ДИГІДРО-4H-ПІРАЗОЛО[3,4-D]ПІРИДИН-4-ОНУ

Вивчено психотропні властивості та взаємодію з речовинами пригнічувального типу нового похідного піримідину - 1-(4-метоксифеніл)-5-{2-[4-(4-метокси-феніл)піперазин-1-іл]-2-оксоетил}-1,5-дигідро-4Н-піразоло [3,4- D]піридин-4-ону в дозі 200 мг/кг, який в попередніх дослідженнях виявив протисудомну дію на рівні вальпроату натрію (300 мг/кг). Встановлено, що сполука чинить виразну седативну дію, виявляє антиамнестичні властивості та слабкий анксіолітичний ефект. Крім того, досліджувана сполука не впливає на депресивну поведінку, не чинить негативного впливу на тонус скелетних м'язів та координацію рухів, а також не потенціює депримуючий вплив етанолу.