Strychnine Research Articles

Three-dimensional flower-like strontium doped zinc oxide decorated with carbon black modified glassy carbon electrode for the detection of strychnine

The widespread use of Strychnine (STN) pesticides has sparked considerable concerns regarding their impact on human health, underscoring the urgent need for a reliable STN detection system to ensure both environmental and human safety. To address this need, a simple hydrothermal technique was employed to synthesize three-dimensional flower-like Strontium doped Zinc oxide (Sr-ZnO) nanomaterials integrated with Carbon Black (CB) to form a composite, which was then utilized for selective STN detection. The prepared Sr-ZnO/CB nanocomposite has been utilized to decorate a glassy carbon electrode (GCE), providing a cost-effective and simplified platform for STN detection. Hence, the structural confirmation of the composite formation was achieved through appropriate microscopic and spectroscopic methods. In terms of electrochemical STN detection, the Sr-ZnO/CB/GCE exhibited superior sensitivity compared to previous sensors. Notably, it demonstrated a broad linearity response range from 0.01 to 145 μM, a low detection limit of 0.02 μM, and a high sensitivity of 5.541 μA μM−1 cm−2 under optimal conditions for STN detection. Hence, the proposed approach showed promise for analyzing STN in biological samples, with satisfactory results obtained when applied to real samples using the Sr-ZnO/CB. Additionally, the Sr-ZnO/CB modified electrode displayed appealing qualities such as stability, repeatability, and suitability for practical applications.

Schisandrin B, a dual positive allosteric modulator of GABAA and glycine receptors, alleviates seizures in multiple mouse models.

Epilepsy is a prevalent and severe neurological disorder and approximately 30% of patients are resistant to existing medications. It is of utmost importance to develop alternative therapies to treat epilepsy. Schisandrin B (SchB) isa major bioactive constituent of Schisandra chinensis (Turcz.) Bailland has multiple neuroprotective effects, sedative and hypnotic activities.In this study, we investigated the antiseizure effect of SchB in various mouse models of seizure and explored the underlying mechanisms. Pentylenetetrazole (PTZ), strychnine (STR), and pilocarpine-induced mouse seizure models were established.We showed that injection ofSchB (10, 30, 60 mg/kg, i.p.) dose-dependentlydelayed the onset of generalized tonic-clonic seizures (GTCS), reduced the incidence of GTCS and mortality in PTZ and STR models. Meanwhile, injection ofSchB (30 mg/kg, i.p.) exhibited therapeutic potential in pilocarpine-induced status epilepticus model, which was considered as a drug-resistant model. In whole-cell recording from CHO/HEK-239 cells stably expressing recombinant human GABAA receptors (GABAARs) and glycine receptors (GlyRs) and cultured hippocampal neurons, co-application of SchB dose-dependently enhanced GABA or glycine-induced current with EC50 values at around 5 μM, and application of SchB (10 μM) alone did not activate the channels in the absence of GABA or glycine.Furthermore, SchB (10 μM) eliminated both PTZ-induced inhibition on GABA-induced current (IGABA) and strychnine (STR)-induced inhibition on glycine-induced current (Iglycine).Moreover, SchB(10 μM) efficiently rescued the impaired GABAARs associated with genetic epilepsies. In addition,the homologous mutants in both GlyRs-α1(S267Q) and GABAARs-α1(S297Q)β2(N289S)γ2L receptors by site-directed mutagenesis testsabolishedSchB-induced potentiation of IGABA and Iglycine. In conclusion, we have identified SchB as a natural positive allosteric modulator of GABAARs and GlyRs, supporting its potential as alternative therapies for epilepsy.

Formulation of Transliposomal Nanocarrier Gel Containing Strychnine for the Effective Management of Skin Cancer.

Strychnine (STCN) has demonstrated an exceptional anticancer effect against various cancers. However, the STCN clinical utility has been hampered by its low water solubility, restricted therapeutic window, short half-life, and significant toxicity. The objective of this investigation was to design and optimize a formulation of strychnine-loaded transliposomes (STCN-TLs) for dermal administration of STCN to treat skin cancer. The formulations of STCN-TL were examined in terms of vesicle size (VS), polydispersity index (PDI), entrapment efficiency (EE), and in vitro delivery. The improved STCN-TL formulation exhibited VS, PDI, EE, and in vitro delivery of 101.5 ± 2.14 nm, 0.218 ± 0.12, 81.74 ± 1.43%, and 85.39 ± 2.33%, respectively. In an ex vivo penetration, the created STCN-TL formulation demonstrated a 2.5-fold increase in permeability compared to the STCN solution. CLSM pictures of skin (rat) revealed that the rhodamine B-loaded transliposome preparation penetrated deeper than the rhodamine B hydroalcoholic mixture. Additionally, rat skin managed with STCN-TL nanogel exhibited a significant increase in Cskin max and AUC0-8 compared to rat skin treated with traditional STCN gel. The findings demonstrated that the transliposome preparation might be a suitable nanocarrier for the cutaneous distribution of STCN in the amelioration of skin cancer.

Evaluation of the anticonvulsant activity of ethanol leaf extract of Panicum maximum in pentylenetetrazole and strychnine induced seizure in mice.

Epilepsy is a chronic neurological condition affecting around 50 million people worldwide. This study evaluated the anticonvulsant effect of Panicium maxmium in pentylenetetrazole (PTZ) and strychnine (STN) induced convulsions in mice. For each model, 25 mice were divided into five groups; group 1 received 10 ml/kg distilled water, groups 2-4 received 100 mg/kg, 200 mg/kg and 400 mg/kg of extract p.o respectively. Group 5 received 3 mg/kg of diazepam p.o. Convulsion was induced intraperitoneally using PTZ and STN, thirty minutes after the extract was administered. The onset of myoclonic, tonic-clonic seizure, time of death within 60 minutes of PTZ and STN administration were monitored. Data were statistically analyzed using one-way ANOVA followed by Dunnet’s comparison tests. In STN-induced seizure model, 100 mg/kg of P. maximum exhibited a significant (p < 0.001) anticonvulsant activity by delaying myoclonic seizure onset in mice when compared to the control. Significant (p < 0.001) activity was also observed in the onset of tonic clonic seizure at same dose when compared to control. In PTZ-induced seizure model, 200 mg/kg exhibited more significant (p < 0.001) activity followed by 100 mg/kg (p < 0.05) by delaying myoclonic seizure onset in mice when compared to the control. Significant (p < 0.001) activity were observed in tonic clonic phase at same doses respectively. The different doses administered couldn’t protect the mice from death. Diazepam, standard drug used, protected all the animals without any signs of convulsions. The results provide evidence that the extract possesses anticonvulsant activity.

Exploring the Antiepileptic Potential of Amaranthus spinosus: An Experimental Study in Albino Mice

About 60% of the world population relies on herbal medicine, and 80% depend almost entirely on it for their primary healthcare. Many of these herbs are rich in phytochemicals, thus valuable as potential sources of drugs. Amaranthus spinosus is a vegetable and ornamental plant used in African folklore to treat several illnesses. This study aimed to investigate the antiepileptic potential of the methanol leaf extract of Amaranthus spinosus in albino mice. Preliminary phytochemical screening and acute toxicity studies were conducted using standard methods. Anticonvulsant studies were conducted using chemo-shock models (pentylenetetrazole (PTZ) - and strychnine (STR)-induced seizures) in mice. Phytochemical screening has revealed the presence of terpenoids, tannins, saponins, alkaloids, anthraquinones, carbohydrates, cardiac glycosides, and flavonoids. Additionally, the acute toxicity studies of the extract revealed that the extract is safe in mice at 2000 mg/kg. The extract at 400 and 800 mg/kg produced a significant (p<0.05) delay in the mean onset of seizures, decreased the duration of seizures induced by PTZ in a dose-dependent manner, and protected the mice. The extract showed insignificant protection against strychnine-induced seizures in mice. This could serve as a scientific basis for further evaluation of the plant’s potential in managing epilepsy, which can lead to the discovery of an effective antiepileptic agent with fewer side effects.

The Synergistic Effect of Fluoxetine, Buspirone, and Sumatriptan with Sodium Valproate and Phenobarbitone in Experimental Models of Convulsion

Epilepsy is one of the most common brain disorders, affecting at least 50 million persons worldwide. Antiepileptic’s have several dose-dependent side effects, necessitating a dose reduction or addition of an adjunct therapy. This study investigates the anticonvulsant activity of low dose phenobarbitone and sodium valproate when combined with buspirone, sumatriptan and fluoxetine. Mice were randomly divided into five groups; group I were treated with 0.2 ml of distilled water, group II were administered 20 mg/kg fluoxetine and 150 mg/kg sodium valproate, group III were administered 20 mg/kg sumatriptan and 150 mg/kg sodium valproate, group IV were administered 5 mg/kg buspirone and 150 mg/kg sodium valproate while group V were administered 150mg/kg of sodium valproate. One hour later, 70 mg/kg pentylenetetrazole (PTZ) was intraperitoneally administered to all mice. The onset of central nervous system (CNS) activity and percentage protection were recorded. The above was repeated using phenobarbitone (15 mg/kg). For strychnine (STN)-induced convulsion, the procedure was repeated with 1 mg/kg strychnine used in place of PTZ. For maximal electroshock shock -induced convulsion, mice were subjected to electroshock current of 50 mA for 0.2 seconds after one hour of administering the drugs as done in the other methods. Sumatriptan and sodium valproate combination significantly delayed the onset of CNS activity when compared with the negative control (p<0.05) in PTZ-induced convulsion. Fluoxetine and buspirone in combination with sodium valproate significantly delayed the onset of CNS activity (p<0.0001) against STN-induced convulsion. The different drugs in combination with phenobarbitone protected the mice against MES and PTZ-induced convulsion.

In Silico and In Vitro Investigation of Phytochemicals Against Shrimp AHPND Syndrome Causing PirA/B Toxins of Vibrio parahaemolyticus.

In Southeast Asia, the penaeid shrimp aquaculture production faces a new pandemic bacterial disease called acute hepatopancreatic necrosis disease (AHPND). The highly profitable pacific white shrimp, Litopenaeus vannamei, has become a challenging species due to severe lethal infections. Recent research has identified a critical pathogen, Vibrio parahaemolyticus, which caused significant loss in the shrimp industry. The disease pathway involves a virulence plasmid encoding binary protein toxins (PirA/B) that cause cell death. The protein toxins were inherited and conjugatively transferred to other Vibrio species through a post-segregational killing system. In this study, "in silico" (Glide, 2021) analysis identified four phytocompounds as myricetin (Myr), ( +)-taxifolin (TF), (-)-epigallocatechin gallate (EGCG), and strychnine (STN) which could be most effective against both the toxins concerning its docking score and affinity. The interactions of complexes and the critical amino acids involved in docking were analyzed using the Discovery Studio (version 2016). Molecular dynamic studies showed lower root mean square deviations (RMSD) and improved stabilization of ( +)-taxifolin (TF) and (-)-epigallocatechin-3-gallate (EGCG) against both the protein toxins. The antibacterial potential of all four selected compounds had tested against pathogenic strains of V. parahaemolyticus through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The best MBC results were observed at concentrations of 1mg/mL for EGCG and 1.25mg/mL for TF. Moreover, the complete reduction of viable cell counts in the in vitro bactericidal activity had recorded after 24h of incubation.

Attenuation of Strychnine-Induced Epilepsy Employing Amaranthus viridis L. Leaves Extract in Experimental Rats.

Epilepsy is one of the most prevalent neurological illnesses defined by periodic seizures with or without loss of consciousness caused by aberrant neural activity. There are many allopathic medications available for the treatment of epilepsy such as phenytoin (PHY), but the side effects are a major concern. Therefore, the present study involved the evaluation of the pharmacological significance of Amaranthus viridis L. extract (EAV) in the management of strychnine (STR)-induced epilepsy. STR (3.5 mg/kg, i.p.) was injected into male rats 30 minutes after the pre-treatment of a standard drug (PHY: 20 mg/kg) and the two doses of EAV (EAV-200 and EAV-400 mg/kg, p.o.) to the respective groups to cause the convulsions. The anti-convulsant effect of EAV-200 and EAV-400 against STR-induced convulsion in rats was investigated in terms of convulsion onset, duration of convulsions, number of convulsions, and convulsion score. Furthermore, the mitochondrial function and integrity in the brain's prefrontal cortex (PFC) were also estimated. EAV-400 significantly increased the onset of convulsion from 61.67 ± 3.051 to 119.2 ± 2.738 and reduced the STR-induced duration of convulsions from 144.8 ± 3.582 to 69.17 ± 3.736, number of convulsions from 4.000 ± 0.1592 to 1.533 ± 0.1542, and convulsion score from 5.000 ± 0.3651 to 2.833 ± 0.3073 in rats. EAV-400 significantly attenuated the STR-induced decrease in the mitochondrial function and integrity of the rat PFC. In rats, EAV-400 significantly accelerated the onset of convulsions while decreasing the STR-induced duration, frequency, and score. Based on investigational findings, EAV-400 could be inferred to be a possible anti-epileptic option for the treatment of epilepsy of this plan in preclinical research.

Antiviral activities of plant-derived indole and β-carboline alkaloids against human and avian influenza viruses

The persistent evolution of drug-resistant influenza strains represents a global concern. The innovation of new treatment approaches through drug screening strategies and investigating the antiviral potential of bioactive natural-based chemicals may address the issue. Herein, we screened the anti-influenza efficacy of some biologically active indole and β-carboline (βC) indole alkaloids against two different influenza A viruses (IAV) with varied host range ranges; seasonal influenza A/Egypt/NRC098/2019(H1N1) and avian influenza A/chicken/Egypt/N12640A/2016(H5N1). All compounds were first assessed for their half-maximal cytotoxic concentration (CC50) in MDCK cells and half-maximal inhibitory concentrations (IC50) against influenza A/H5N1. Intriguingly, Strychnine sulfate, Harmalol, Harmane, and Harmaline showed robust anti-H5N1 activities with IC50 values of 11.85, 0.02, 0.023, and 3.42 µg/ml, respectively, as compared to zanamivir and amantadine as control drugs (IC50 = 0.079 µg/ml and 17.59 µg/ml, respectively). The efficacy of the predefined phytochemicals was further confirmed against influenza A/H1N1 and they displayed potent anti-H1N1 activities compared to reference drugs. Based on SI values, the highly promising compounds were then evaluated for antiviral efficacy through plaque reduction assay and consistently they revealed high viral inhibition percentages at non-toxic concentrations. By studying the modes of antiviral action, Harmane and Harmalol could suppress viral infection via interfering mainly with the viral replication of the influenza A/H5N1 virus, whilst Harmaline exhibited a viricidal effect against the influenza A/H5N1 virus. Whereas, Strychnine sulfate elucidated its anti-influenza potency by interfering with viral adsorption into MDCK cells. Consistently, chemoinformatic studies showed that all studied phytochemicals illustrated HB formations with essential peptide cleft through the NH of indole moiety. Among active alkaloids, harmalol displayed the best lipophilicity metrics including ligand efficiency (LE) and ligand lipophilic efficiency (LLE) for both viruses. Compounds geometry and their ability to participate in HB formation are very crucial.

An experimental evaluation of anticonvulsant activity of aqueous extract of Caralluma dalzielii N.E. Brown

Ethnopharmacological RelevanceCaralluma dalzielii belongs to the family of Asclepiadiaceae. It is a succulent perennial plant widely distributed across the Sahel region from Senegal to Northwest Nigeria. Extracts from Caralluma dalzielii are used traditionally in the treatment of pain, infertility, epilepsy and other neurological diseases. Aim of the studyThe aim of the present study was to evaluate the anticonvulsant effects of aqueous extracts of aerial parts of Caralluma dalzielii using various experimental models. Materials and methodsThe anticonvulsant effect of the plant extract (250, 500 and 1000 mg/kg p.o) were assessed using maximal electroshock (MES) model in chicks, pentylenetetrazole (PTZ) and strychnine (STN)-induced seizures models in mice. Diazepam-induced sleep in chicks was used to study the sedative property of the plant. In the anticonvulsant and sedative property studies, the onset and duration of seizures and sleep were recorded respectively. The oral acute toxicity study was assessed. The extract was screened preliminarily for its phytochemicals and was further analysed using Gas chromatography-mass spectrometry (GC–MS) to identify its major chemical components. ResultsThe oral acute toxicity studies showed that the LD50 was greater than 5000 mg/kg in mice. Pre-treatment of mice with the aqueous extract of Caralluma dalzielii produced a dose-dependent protection against PTZ-induced seizures and mortality with 100% protection at the highest dose of the extract. The extract also significantly increased the latency/onset of myoclonic jerks and reduced the duration of tonic seizures dose dependently. In STN-induced seizure, the extract had no protection against seizure induction similar to diazepam the positive control. However, it significantly (p < 0.05) prolonged the latency of seizure and increased the survival time before death in a dose dependent manner. Caralluma dalzielii had zero protection against maximal electroshock. Phytochemical screening showed the presence of flavonoids, tannins, saponins, steroids, glycosides, cardiac glycosides and phenols. GC–MS analysis revealed the presence of some compounds. ConclusionThe extract of Caralluma dalzielii possesses anticonvulsant activity with less marked sedative activity. It also contains several phytochemicals which may be responsible for the activity. This study serves to validate the use of this plant in folkloric medicine for the treatment of epilepsy and convulsions.

Revealing the most effective anticonvulsant part of Malvaviscus arboreus Dill. Ex Cav. and its acute and sub-acute toxicity

Ethnopharmacology relevanceDifferent parts of Malvaviscus arboreus Dill. Ex Cav. (M. arboreus) are traditionally used in the West Region of Cameroon to treat many diseases, including epilepsy. Aim of the studyTo determine which part of M. arboreus offers the best anticonvulsant effect, and to assess the acute and sub-acute toxicity of the part of interest. Materials and methodsthe anticonvulsant effect of the aqueous lyophilisate of the decoction of flowers, leaves, stems and roots of M. arboreus at various doses was evaluated and compared on the model of acute epileptic seizures induced by pentylenetetrazole (PTZ) (70 mg/kg), injected 1 h after oral administration of the various extracts. Out of these plant parts, the leaves were then selected to prepare the hydroethanolic extract and its anticonvulsant effect against PTZ at the doses of 122.5, 245 and 490 mg/kg, as well as its acute toxicity were compared with those of the aqueous lyophilisate of the leaves. The anticonvulsant effect of the aqueous lyophilisate of M. arboreus leaves was further evaluated on models of acute epileptic seizures induced by picrotoxin (PIC) (7.5 mg/kg), strychnine (STR) (2.5 mg/kg) and pilocarpine (350 mg/kg). The 28 days sub-acute toxicity, as well as the quantitative phytochemistry and the in vitro antioxidant potential (FRAP, DPPH, ABTS+) of the aqueous lyophilisate of the leaves of M. arboreus were also evaluated. ResultsM. arboreus leaves showed the best anticonvulsant effect and the aqueous lyophilisate was the best extract. The latter significantly protected the animals against convulsions induced by PTZ (71.43%) (p < 0.01), PIC (57.14%) (p < 0.05) and STR (42%) and had no effect on pilocarpine-induced seizures. Furthermore, it showed no acute or sub-acute toxicity, and revealed a high content of flavonoids, saponins, tannins and alkaloids, and antioxidant activity in vitro. ConclusionThe aqueous lyophilisate of the leaves of M. arboreus offers the best anticonvulsant effect on the extraction solvent used, and it would act mainly via a potentiation of the inhibitory systems of the brain (GABA, Glycine). In addition, its richness in bioactive compounds gives it an antioxidant potential, and it is not toxic in acute and sub-acute toxicity. All this justifies at least in part its empirical uses, and makes M. arboreus a candidate for the alternative treatment of epilepsy.

Gas Chromatography‐Mass Spectrometry Analysis and Neuropharmacological Evaluation of Aqueous Extract of Aerial Parts of Caralluma dalzielii N E Brown

IntroductionCaralluma dalzielli (Asclepiadiaceae) is a succulent perennial plant that is widely distributed across the Sahel region of West Africa. Decoctions from the plant are used traditionally for treating infertility, epilepsy and neurological diseases. The aim of the present study was to evaluate some neurological effects of aqueous extract of aerial parts of Caralluma dalzielii (APCD) in mice and to analyse its components through Gas chromatography‐mass spectrometry (GC‐MS).Materials and methodsThe effect of the APCD (100, 200 and 400 mg/kg p.o) on motor coordination, sedation and anxiety in mice were assessed using three models, namely, beam walk assay, staircase test and hole‐board test. Its anticonvulsant activity was assessed in pentylenetetrazole (PTZ) and strychnine (STN)‐induced seizures in mice. Beam walk assay measured the number of foot slips of the mice, staircase test, measured the number of rearing for each mouse over a 5‐min period while the hole‐board test measured the number of head dips of the mice during a 5‐min period. In the anticonvulsant study, the onset and duration of seizures were recorded. Phytochemical screening was carried out according to standard procedures. APCD was subjected to further analysis using GC‐MS to identify its major components.ResultsAn increase in the number of foot slips is regarded as having peripheral muscle relaxant and sedative activities, however, APCD at all doses showed no significant increase in the number of foot slips. Increase in the number of rearing is a characteristic of anxiety. APCD at all doses significantly (p&lt;0.05) reduced the number of rearing suggesting anxiolytic activity. The behavioural episode of head dipping was used for assessing anxiolytic activity. Increase in the number of head dips described anxiolysis. The extract showed a significant (p&lt;0.05) increase the number of head dips at all dose levels. Pre‐treatment of mice with APCD produced a dose‐dependent protection against PTZ‐induced seizures with 100% protection at the highest dose of APCD. APCD also significantly (p&lt;0.05) increased the latency/onset of myoclonic jerks and reduced the duration of tonic seizures dose dependently. In STN‐induced seizure, APCD significantly (p&lt;0.05) prolonged the latency of tonic seizure and increased the survival time before death in a dose dependent manner. Phytochemical analysis of the extract showed the presence of alkaloids, flavonoids, tannins, saponins, steroids, cardiac glycosides and phenols. GC‐MS analysis revealed 85 compounds of which the major ones were Heptadecene (6.99%), Octadecene (6.83%), 2‐Amino‐5‐methylbenzoic acid (5.17%), 1‐Butoxy‐2,4‐dimethyl‐2‐pentene (4.97%), Benzene propanoic acid (4.89%), Hexadecanoic acid (3.94%), 2,4‐Di‐tert‐butylphenol (3.233%) and 1‐Tetradecanol (2.16%).ConclusionAPCD possesses neuropharmacological properties with anxiolytic and anticonvulsant activities but without prominent effect on motor coordination. The presence of various phytochemical constituents may be responsible. This report validates the ethnomedicinal use of the plant for the treatment of neurological diseases.

Role of Gabanergic and, or Serotonergic in the Anti-seizure Activity of Methanol Extract of Crinum jagus (J. Thomps) in Experimental Mice

Objective: Crinum jagus is used in traditional African medicine in the treatment of epilepsy, pain and inflammations.&#x0D; Methods: Anticonvulsant activity was investigated using picrotoxin (PCT) and strychnine (STR) tests in experimental paradigm.&#x0D; Results: Crinum jagus leaf methanol extract (200, 400, and 800 mg kg−1) potentiated hexobarbitone-induced sleeping time and significantly (p&lt;0.05) shortened the duration of convulsions in PCT-induced seizures. Delay in the onset of convulsions in PCT-induced seizure were very significant (p&lt;0.05). Reduction in the frequency of seizures was also significant (p&lt;0.05) in the test. Diazepam (5 mg kg−1) was used as reference anticonvulsant drugs in the experimental models. While, CJB failed to protect the animals against picrotocin-induced convulsion. Neither the extract of CJL nor CJB confer significant effect on STR-induced convulsion. Flumazenil (GABA receptor antagonist) and cyproheptadine (5-HT2 receptor antagonist) blocked the effect of CJL extract in the PCT tests significantly suggesting that Crinum jagus may be acting by enhancing the effects of the GABAergic and serotonergic systems.&#x0D; Conclusion: The data obtained suggest that methanol leaf extract of C. jagus possessed significant anticonvulsant effect, thereby confirming the traditional uses of C. jagus in the treatment of epilepsies; mechanisms of which may involve interaction with GABAergic and serotonergic pathway.

The Production and Evaluation of an Electrochemical Sensors for Strychnine and Its Main Metabolite Strychnine N-Oxide for Their Use in Biological Samples.

Strychnine (STN) and its major metabolite Strychnine N-Oxide (SNO) were examined electrochemically. Both parent compounds and its major metabolite showed electroactivity on glassy carbon electrodes using CV and DPV techniques. One oxidation peak at 1008 mV was observed for STN with the optimum peak intensity at pH 7. SNO produced two oxidation peaks, at 617 mV and 797 mV, at pH 5. The peaks demonstrated irreversible behaviour and the irreversibility of the system was confirmed at different scan rates. A calibration curve was produced for both CV and DPV measurements and the sensitivity of the proposed EC method was good compared with previous electrochemical and non-electrochemical methods. The precision of oxidation peak of STN using the STN-MIP method produced a maximum value of 11.5% and 2.32% for inter-day and intraday %RSD, respectively. The average% recovery was around 92%. The electrochemical method has been successfully applied to the determination of STN in spiked plasma and urine samples. For SNO, both anodic peaks of SNO demonstrated irreversible behaviour. A different sweep rate was used for calculating the number of ‘transfer electrons’ in the system; based on this, the mechanism of oxidation reaction was proposed. Calibration curves for both oxidative peaks were produced using DPV measurements. The second anodic peak demonstrated high linearity and precision with %RSD < 1.96%.

The Eight Hydrates of Strychnine Sulfate.

Commercial samples of strychnine sulfate were used as the starting material in crystallization experiments accompanied by stability studies. Eight hydrate forms (HyA–HyG), including five novel hydrates, were verified. The crystal structures of HyA (“pentahydrate”) and HyF (“hexahydrate”) were determined from single-crystal X-ray diffraction data. HyF was identified as the most stable hydrate at high water activities at room temperature (RT), and HyA and HyC were also found to be stable at ambient conditions. Long-time storage experiments over nearly two decades confirm that these three hydrates are stable at ambient conditions (20–60% relative humidity). The other five hydrates, HyB (“dihydrate”), HyD, HyE, HyG, and HyH, are only observable at the low(est) relative humidity (RH) levels at RT. Some of these latter forms can only exist within a very narrow RH range and are therefore intermediate phases. By applying a range of complementary experimental techniques such as gravimetric moisture sorption analysis, thermal analysis, moisture controlled PXRD measurements, and variable temperature IR spectroscopy in combination with principal component analysis, it was possible to identify the distinct hydrate phases and elucidate their stability and dehydration pathways. The observed (de)hydration routes, HyA ↔ HyB, HyC ↔ HyD ↔ HyE, HyF ↔ HyG ↔ HyH and HyF → HyA ↔ HyB, depended on the initial hydrate form, particle size, and atmospheric conditions. In addition, a transformation from HyC/HyA to HyF occurs at high RH values at RT. The specific moisture and temperature conditions of none of the applied drying regimes yielded a crystalline water-free form, which highlights the essential role of water molecules for the formation and stability of the crystalline strychnine sulfate phases.

Anticonvulsant Potential of Dichloromethane Extract of Aspilia africana Leaf in Mice

Aim: The study was carried out to determine the anticonvulsant potential of dichloromethane leaf extract of Aspilia africana.&#x0D; Study Design: Three seizure models namely: Pentylenetetrazole (PTZ), strychnine (STC) and maximal electroshock (MES) were used, motor coordination behavior of the animals were also assessed.&#x0D; Place and Duration of Study: The study was carried out between the months of October and November, 2017 at Pharmacology laboratory, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria.&#x0D; Methodology: The powdered leaves of A. africana (2000 g) were extracted with 10 liters of 100% dichloromethane. Doses of 25, 50, 100 and 200 mg/kg were administered to the test animals.&#x0D; Results: The chemical models, STC &amp; PTZ showed 50% &amp; 100% survival respectively. The delayed onset of seizure suggested anti-seizure potential of dichloromethane extract of A. Africana leaf with the maximal latency period of seizure recorded in the 25 mg/kg dose within the following chemical models, this was significant, P = .05 compared to the normal control. The MES method showed that at doses of 25 &amp; 50, 100 mg/kg, the animals were 66.7% &amp; 50% free of hind limb tonic extension (HLTE). Furthermore, there was reduced motor coordination potential at 25 mg/kg by 68.5%, which was significant at the level of, P = .05, compared to healthy control. &#x0D; Conclusion: From the preceding, it can be seen that the dichloromethane leaf extract of A. Africana has antiseizure potential.

Immunomodulatory activity of marine natural products: Synthesis, spectral characterization and toxicity assessment of natural and related synthetic iodinated tyramides

The toxicity of natural marine iodoarenes or their synthetic counterparts is widely unknown despite the fact that triiodothyronine and thyroxine are members of this class. In this work we aimed to expand such knowledge on iodinated marine natural products and tested an ascidian (Didemnum rubeum) metabolite, N-(3,5-diiodo-4-methoxyphenethyl)benzamide, together with closely related synthetic iodinated tyramides: N-(2,5-diiodo-4-methoxyphenethyl)benzamide, N-(3-iodo-4-methoxyphenethyl)benzamide, N-(4-methoxyphenethyl)benzamide, and N-(3-iodo-4-methoxyphenethyl)formamide, for their effect on the viability of rat macrophages, as well as acute toxicity on Artemia salina. The tested tyramides exerted a varying degree of toxicity towards brine shrimps, but in certain cases, the determined lethal concentrations were even lower than those of known toxicants (e.g. strychnine sulfate, SDS). The toxicity was highly dependent on the structure of these mutually related compounds, while the natural one was shown to be the most toxic. In the case of macrophage cultures, the tested tyramides exerted much less toxicity but were found to have an effect on the functioning of these normal immune cells. The samples of the tyramides were obtained by synthesis, and were fully structurally and spectrally characterized, which also provided corroboration of the proposed structure of the natural product originally isolated in minute amounts.

EVALUATION OF ANTICONVULSANT ACTIVITY OF PREMNA HERBACEA (ROXB.) ROOT EXTRACTS IN ISONIAZID AND STRYCHNINE-INDUCED CONVULSIONS

Objective: The present investigation was to evaluate the anticonvulsant potential of three different extracts of roots of Premna herbacea (Roxb.) in mice. The preclinical screening models such as isoniazid (INH)- and strychnine (STR)-induced convulsion were selected for the study.Methods: The three different extracts of P. herbacea, i.e., ethanolic (PHE), petroleum ether (PHP), and chloroform (PHC) were prepared as per standard procedures and evaluated at three different doses (100, 200, and 400 mg/kg) and screened with above-mentioned INH and STR-induced convulsions.Results: In INH model, PHC 200 mg/kg and 400 mg/kg showed dose-dependent delay in onset of convulsion (p&lt;0.05 and p&lt;0.01) along with protection of 33.33% of mice. The PHP 400 mg/kg also showed a significant delay in the onset of convulsion (p&lt;0.05) along with protection of 16.66% of mice. In STR-induced model, none of the extracts was effective to delay the onset of convulsion; however, PHC 400 mg/kg protected 16.66% of mice.Conclusion: The results confirmed dose-dependent anticonvulsant activity of P. herbacea PHC in INH-induced convulsions.

Studies on Anticonvulsant Effects of Novel Histamine H3R Antagonists in Electrically and Chemically Induced Seizures in Rats.

A newly developed series of non-imidazole histamine H3 receptor (H3R) antagonists (1–16) was evaluated in vivo for anticonvulsant effects in three different seizure models in Wistar rats. Among the novel H3R antagonists examined, H3R antagonist 4 shortened the duration of tonic hind limb extension (THLE) in a dose-dependent fashion in the maximal electroshock (MES)-induced seizure and offered full protection against pentylenetetrazole (PTZ)-induced generalized tonic-clonic seizure (GTCS), following acute systemic administration (2.5, 5, 10, and 15 mg/kg, i.p.). However, only H3R antagonist 13, without appreciable protective effects in MES- and PTZ-induced seizure, fully protected animals in the strychnine (STR)-induced GTCS following acute systemic pretreatment (10 mg/kg, i.p.). Moreover, the protective effect observed with H3R antagonist 4 in MES-induced seizure was completely abolished when animals were co-administered with the H3R agonist (R)-α-methylhistamine (RAMH, 10 mg/kg, i.p.). However, RAMH failed to abolish the full protection provided by the H3R antagonist 4 in PTZ-induced seizure and H3R antagonist 13 in STR-induced seizure. Furthermore, in vitro antiproliferative effects or possible metabolic interactions could not be observed for compound 4. Additionally, the predictive in silico, as well as in vitro, metabolic stability for the most promising H3R antagonist 4 was assessed. The obtained results show prospective effects of non-imidazole H3R antagonists as innovative antiepileptic drugs (AEDs) for potential single use against epilepsy.

Electrosprayed Nanosystems of Carbamazepine - PVP K30 for Enhancing Its Pharmacologic Effects.

This study was conducted to enhance the pharmacologic effect of carbamazepine (CBZ) (as a poorly water-soluble drug) by fabricating CBZ-PVP K30 nanobeads using an electrospraying technique. CBZ-PVP K30 nanosystems with various ratios (1:3 and 1:5) at total solution concentrations of 3% and 5% w/v were prepared. The solution concentration extremely affected the size of the samples; where, the nanobeads (mean diameter of 457.65 ± 113.72 nm and 1.16 ± 0.46 µm) were developed at low and high solution concentrations, respectively. DSC thermographs and PXRD patterns precisely showed CBZ amorphization in the electrosprayed nanosystems. Based on the FTIR spectrum of the electrosprayed samples, a feasible interaction between N-H/O-H group of CBZ and PVP carbonyl group was detected. The in-vitro release studies revealed that the electrosprayed nanosystems represent a comparable rapid dissolution rate with respect to the physical mixtures (PMs) and the pure drug. The in-vivo results in NMRI mice indicated that the electrosprayed nanoformulation (with the drug: polymer ratio of 1:5 at a total solution concentration of 5% (w/v)) prolonged seizure latency time and decreased mortality percent in strychnine (STR) induced seizure mice more efficiently than the PM. Our finding revealed that the electrospraying as a cost-benefit and one step technique could be effectively applied for improving the physicochemical characteristics and pharmacologic effect of CBZ.