Antinociceptive activities of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol, and its possible mechanisms of action in mice

A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC’s ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.

MORPHOLOGICAL MANIFESTATIONS OF EXPERIMENTAL PACLITAXEL-INDUCED SICK NERVE NEUROPATHY UNDER CORRECTION OF 2-ETHYL-6-METHYLIDE-3-HYCYDYR-3-HYDYCIDE-3

Paclitaxel is an effective chemotherapeutic agent for many cancers, but has a number of limiting side effects that not only significantly reduce the quality of life of patients, but also limit their further treatment. Peripheral neuropathy is one of these, but as of today, there are no proven effective drugs for the prevention or treatment of paclitaxel-induced neuropathic pain (IDP) in particular, or peripheral chemotherapy-induced neuropathy (PIH) in general. 2-ethyl-6-methyl-3-hydroxypyridine succinate (HS) is a derivative of succinic acid with neuroprotective, antihypoxic, membrane-protective, nootropic, sedative action. The experiment was performed on 80 white rats injected intraperitoneally with paclitaxel (Actavis, Romania), pre-dissolved in isotonic saline at a dose of 2 mg / kg body weight four times a day until a total dose of 8 mg / kg. Forty of these animals were then injected intraperitoneally with 2-ethyl-6-methyl-3-hydroxypyridine succinate at a dose of 10 mg / kg (the other 40 rats received intraperitoneal water for injection). Morphological studies were performed on the 1st, 7th, 15th, 28th, 60th, 90th and 120th days after the last administration of the drug. We investigated the pharmacological potential of HS in the prevention and treatment of PNH at the level of the sciatic nerve (CH). Our results allow us to conclude that the introduction of HS creates a protective effect against paclitaxel-induced peripheral neuropathy (PIPN) by affecting both the axial cylinder and the myelin sheath of HF. Due to the known pathophysiological mechanisms of neuropathy, this method can be a promising therapeutic tool for the prevention and treatment of PIPN.

Study of the sedative effect of extract from tissue culture biomass of Rauwolfia serpentina

Several social, psychological and biological factors could be cause for central nervous system disorders, especially anxiety; the latter could lead to more serious neurological and psychosomatical disorders. Sedative medications of plant origin are widely used practically as an alternative and/or additive to traditional pharmacological treatments of anxiety, hyperexcitation and other neuroses. Thus, the search of new effective sedatives based on plant extracts is an actual and perspective task. Aim of the present work is to investigate the sedative effect of biomass extract from cell culture of Rauwolfia serpentina K-27 strain. Sedative action of biomass extract from cell culture of Rauwolfia serpentina high-productive strain was determined by open field method on 24 white mice males (no line). Mice weight was in 18–25 g interval. The behavior was assessed by usual behavioristic acts: motor activity, psychoemotional activity and tentative research reaction. Animals were randomized into 3 groups of 8 individuals each. Rauwolfia serpentina biomass extract at doses of 7.5 mg/kg (group 1) or 15 mg/kg (group 2) was administered orally as an aqueous solution. Animals of the control group (group 3) received a solvent (distilled water). The sedative effect of extract was discovered in doses of 7.5 and 15 mg/kg, that showed a decrease in horizontal motor activity to 63.31 and 79.76% respectively, vertical activity to 82.05 and 71.79%, grooming duration to 57.28 and 60.78% at experimental days 20 to 28. Tentative research reaction demonstrated the direct dependence of sedation intensity on duration of extract administration. As a result of the conducted researches significant differences in the number of fecal bolus of both experimental and control groups of mice were not revealed. No significant difference between the sedative effect and the dose (7.5 and 15 mg/kg) was observed. The sedative effect of biomass extract from cell culture of Rauwolfia serpentina K-27 strain was proven. This leads to perspective inclusion of the extract to traditional medicine in prophylaxis and treatment of insomnia and of physical and psychological overexcitation.

Hopantomide in pediatric neurological practice: outlooks

Hopantomide® is a drug containing calcium salt of hopantenic acid. The drug is registered and produced in Russia (Usolye-Siberian Chemical Pharmaceutical Factory) with the use of own raw materials and goes through a full production cycle, which guarantees quality control at every stage. Hopantomide belongs to nootropics and has neurometabolic, neuroprotective, and neurotrophic properties, as well as anticonvulsant action. According to the package insert and results of the studies evaluating the efficacy of hopantenic acid, Hopantomide has a number of positive therapeutic effects. It increases brain resistance to hypoxia and toxic substances, stimulates anabolic processes in neurons, improves mental and physical performance, combines moderate sedative action with mild stimulating effect, reduces motor excitability with simultaneous regulation of behavior, improves the metabolism of gamma-aminobutyric acid and normalizes its level in individuals with chronic alcohol intoxication and after alcohol withdrawal, has anxiolytic and thymoleptic properties, inhibits the abnormal bladder reflex and detrusor tone. This ensures high efficacy of Hopantomide in the treatment of various nervous diseases in different age groups. In our opinion, the combination of various positive effects of just one drug can significantly reduce the pharmacological burden. In this review, we discuss well-known and potential mechanisms of action, indications for its use with a focus on Hopantomide benefits in pediatric neurological practice, and studies evaluating the efficacy of hopantenic acid in clinical practice. Particular attention is paid to the possibilities of its use in children, including those with attention deficit hyperactivity disorder and developmental delay, as well as the part of combination therapy for epilepsy together with antiepileptic drugs.Drugs containing hopantenic acid are well tolerated by patients, including children who receive it for a long time.

Identification of clinical phenotypes in schizophrenia: the role of lurasidone

The treatment of schizophrenia includes the control of symptoms, the prevention of relapses, and amelioration of adaptive skills for patient re-integration into society. Antipsychotic drugs are the agents of choice for the treatment of schizophrenia, as they reduce the positive symptoms of psychosis. Lurasidone is a second-generation antipsychotic drug representing a novel and useful clinical tool for the management of schizophrenia. A board consisting of a panel of Italian expert psychiatrists was organized with the following aims: (a) defining the current modalities of use of lurasidone, highlighted through 17 specific questions; (b) defining and agreeing the main features of the drug and the principal reasons to suggest its administration. We established that lurasidone is suggested at any age, with no gender difference, at all stages of the disease. The switch from previous treatments is done primarily because of lack of efficacy as well as poor adherence/tolerability. Lurasidone is among the best-tolerated antipsychotics, and its use is indicated in the presence of different comorbidities. A wide range of dosages is available, allowing safe titration in particular cases, with the highest dose (148 mg) generally used for the treatment of the acute phase. The discontinuation rate due to poor tolerability, low compliance, and interactions with other drugs is very low. Akathisia is the most reported adverse event, but it may be controlled by dose reduction. Lurasidone does not possess a marked sedative action but, in agitated patients, can be associated with sedative drugs, such as benzodiazepines. The most frequent reason for switching to other therapies is the need for long-acting formulations, as in patients at risk of very low adherence or suicide. Lurasidone does not strongly impact metabolism or the cardiovascular system (QT interval), and does not influence the metabolism of other drugs, showing good efficacy and tolerability.

Synthesis of Surfactants Derived from 2-Mercaptobenzimidazole and Study of Their Acute Toxicity and Analgesic and Psychotropic Activities

The aim of the present study is to synthesize cationic salts from a relatively toxic compound named 2-mercaptobenzimidazole and to evaluate some of their pharmacological properties. The acute toxicity of these salts is evaluated according to OECD 423 Guidelines at the doses of 300 and 2000 mg/kg; their peripheral analgesic effect is studied using the Koster test at the therapeutic dose of 200 mg/kg and their sedative action is evaluated using Traction, Chimney, Hole-board, and Rotarod tests at the doses of 200 and 400 mg/kg. All synthesized molecules show no acute toxicity according to OECD Code 423 guidelines at doses ranging from 300 to 2000 mg/kg and do not cause any obesity or anorexia. Also, the results of the Koster test show that the studied compounds have an average analgesic effect at the dose of 200 mg/kg compared to acetylsalicylic acid. In addition, the elaborated compounds have shown a moderate sedative effect at the dose of 400 mg/kg, in comparison to 2-mercaptobenzimidazole (400 mg/kg) and Bromazepam (20 mg/kg). These compounds have no cataleptic and hypnotic effects on the central nervous system at the doses of 200 and 400 mg/kg. These results argue in favor of a possible integration of the most active salts tested in the pharmaceutical industry owing to their analgesic and sedative effects.

Tarczyca bocznokwiatowa (Scutellaria lateriflora) – znaczenie w medycynie tradycyjnej i pozycja we współczesnej fitoterapii

American skullcap (Scutellaria lateriflora L.) has long been used as a medicine by North American Indian tribes. A monograph of Scutellariae lateriflorae herba was included in the American Herbal Pharmacopoeia in 2009. This raw material is very popular in North America because of its sedative action. It is also highly valued in Australia, while in Europe, it has been widely used until now in the United Kingdom. The main components of the herb of this plant species include flavonoids specific for the Scutellaria genus, mostly baicalein, baicalin, wogonin, scutellarin. They are accompanied by other groups of compounds: diterpenoids – neoclerodan derivatives, γ-aminobutyric acid, melatonin, serotonin, catalpol, phenolic acids, phenylpropanoid glycosides (mostly verbascoside) and essential oil. Studies of chemical composition and investigation of medicinal activity of this raw material confirmed its uses known from North American folk medicine. Study results proved most of all a significance of flavonoid compounds present in the raw material for its documented biological activity. The aim of the paper is to review the present knowledge on chemical composition and medicinal significance of this very valuable plant. The research team from the Department of Pharmaceutical Botany JU MC initiated biotechnological studies of this species. Its microshoots successfully grown in vitro produce considerable amounts of specific flavonoids (mostly baicalin and wogonoside) and verbascoside, and in future they can be an alternative rich source of these compounds for pharmaceutical and cosmetic applications.

FORMULATION AND EVALUATION OF DIAZEPAM-LOADED INTRAVAGINAL ALGINATE BEADS: AN INVESTIGATION STUDY FOR THE TREATMENT OF PELVIC FLOOR DYSFUNCTION

Objective: The fundamental objective of this research investigation was to develop intravaginal diazepam (DZ)-loaded alginate beads for the management of acute pelvic floor dysfunction (PFD) pain with minimal sedative effect.Methods: DZ loaded beads were prepared by an ionotropic gelation method using SA (sodium alginate) alone, or in combination with either poloxamer 407 (PL), pectin (PC), or xanthan gum (XG) at different ratios in the presence of different concentrations of calcium chloride as a cross-linking agent. The successfully developed beads were evaluated for the particle size, pH, yield percentage, entrapment efficiency, in vitro bioadhesion, swelling percentage, and in vitro drug release. The stability, ex vivo drug permeation, and sedative action of the optimized beads formulations were studied.Results: The particle size of the formulated beads was from 395±3.3 to 515±2.8 μm, yield percentage was from 68.2±1.7 to 87.5±2.1, entrapment efficiency was from 65.6±1.6 to 87.5±2.1. pH ranged from 6.1±0.2 to 6.8±0.6, bioadhesion strength was from 71.5±1.3 to 87.6±3.1, and swelling percentage was in the range from 53.4±3.1 to 85.2±3.7. Approximately 92.4–72.6% of the loaded dose was released from the prepared beads. The optimized beads showed a good stability under the selected storage conditions. About 74.8%, 71.1%, 68.6%, and 63.4% of the loaded dose permeated through the rabbit vaginal mucosa from F7, F9, F3, and F11, respectively. The formulated beads decreased the sedative action associated with orally or parenterally administered DZ.Conclusion: The developed beads were considered a promising candidate to formulate DZ into a new dosage form for the treatment of PFD with a minimum central nervous system sedation.