Extract Depresses Excitatory Synaptic Transmission and Chemically-Induced Seizures in the Rat Hippocampus.

Extracts of the tropical Cinderella plant are used traditionally to manage convulsive conditions in the West African sub-region. This study sought to determine the neuronal basis of the effectiveness of these plant extracts to suppress seizure activity. Using the hippocampal slice preparation from rats, the ability of the extract to depress excitatory synaptic transmission and seizure activity were investigated.

A novel oxazolidinone derivative PH192 demonstrates anticonvulsant activity in vivo in rats and mice.

The pharmacotherapeutic management of seizure disorders with currently available medications is not optimal due to side effects and failure of some patients to respond to all available medications. As such there is the need to develop new antiseizure drugs by looking at new chemical classes of compounds. We recently screened, in vitro, a new class of compounds, the oxazolidinones, for actions in the brain that may indicate potential for antiseizure activity.

Extract of Synedrella nodiflora (L) Gaertn exhibits antipsychotic properties in murine models of psychosis.

Background: The hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) has demonstrated anticonvulsant, sedative and analgesic effects. Preliminary studies conducted in animals, SNE significantly decreased stereotypic behaviours suggesting antipsychotic potential. Coupled with the central nervous system depressant effects of SNE, we hypothesized that it may have utility in the management of psychosis.

Blood concentration of prilocaine and lidocaine after the use of topical anesthesia (Oraqix ) in lacerated wounds.

Background/aim: Soft tissue injuries have been reported as being sutured using only topical anesthesia applied in the laceration wound. The objective of this study was to assess the pharmacokinetic profile of components of Oraqix (2.5% prilocaine and 2.

Paclitaxel Causes Electrophysiological Changes in the Anterior Cingulate Cortex via Modulation of the γ-Aminobutyric Acid-ergic System.

Objective: The aim of this study was to elucidate any electrophysiological changes that may contribute to the development of neuropathic pain during treatment with the anticancer drug paclitaxel, particularly in the γ-aminobutyric acid (GABA) system.

Materials And Methods: One hundred and eight Sprague-Dawley rats were used (untreated control: 43; vehicle-treated: 21, and paclitaxel-treated: 44). Paclitaxel (8 mg/kg) was administered intraperitoneally on 2 alternate days to induce mechanical allodynia.

Parenteral nutrition in hospital pharmacies.

Purpose - The purpose of this paper is to explore parenteral nutrition (PN) practices in hospital pharmacies of Kuwait and identify potential avenues for quality improvement in this service. Design/methodology/approach - A descriptive, qualitative study about PN practices was conducted from June 2012 to February 2013 in Kuwait. Data were collected via in-depth semi-structured interviews with the head total parenteral nutrition (TPN) pharmacists at seven hospitals using a developed questionnaire.

Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice.

Recently, we found that methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), an anticonvulsant enaminone, has antinociceptive activity in the hot plate test. In this study we evaluated the antinociceptive activity of five anilino enaminones E139, ethyl 4-(4'-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E121), ethyl 4-(4'-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E122), methyl 4-(4'-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E138) and ethyl 4-(4'-fluorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (BRG 19) using the formalin and hot plate tests. E139 has been reported to exert its effects via enhancement of extracellular GABA levels, thus tiagabine, a GABA transporter inhibitor, was evaluated as a control together with indomethacin.

Pharmaceutical care education in Kuwait: pharmacy students' perspectives.

Background: Pharmaceutical care is defined as the responsible provision of medication therapy to achieve definite outcomes that improve patients' quality of life. Pharmacy education should equip students with the knowledge, skills, and attitudes they need to practise pharmaceutical care competently.

Objective: To investigate pharmacy students' attitudes towards pharmaceutical care, perceptions of their preparedness to perform pharmaceutical care competencies, opinions about the importance of the various pharmaceutical care activities, and the barriers to its implementation in Kuwait.

Pharmaceutical care in Kuwait: hospital pharmacists' perspectives.

Background: Pharmaceutical care practice has been championed as the primary mission of the pharmacy profession, but its implementation has been suboptimal in many developing countries including Kuwait. Pharmacists must have sufficient knowledge, skills, and positive attitudes to practise pharmaceutical care, and barriers in the pharmacy practice model must be overcome before pharmaceutical care can be broadly implemented in a given healthcare system.

Objective: To investigate hospital pharmacists' attitudes towards pharmaceutical care, perceptions of their preparedness to provide pharmaceutical care, and the barriers to its implementation in Kuwait.

Evaluation of anticonvulsant actions of dibromophenyl enaminones using in vitro and in vivo seizure models.

Epilepsy and other seizure disorders are not adequately managed with currently available drugs. We recently synthesized a series of dibromophenyl enaminones and demonstrated that AK6 and E249 were equipotent to previous analogs but more efficacious in suppressing neuronal excitation. Here we examined the actions of these lead compounds on in vitro and in vivo seizure models.

Synthesis, neuronal activity and mechanisms of action of halogenated enaminones.

Due to the excellent anticonvulsant activity of previously synthesized halogenated enaminones, more disubstituted analogs were synthesized and evaluated in vitro. The new enaminones either had no effect, depressed, or enhanced population spike (PS) amplitude in the rat hippocampus in a concentration-dependent manner. Structure-activity relationship (SAR) analysis indicated that compounds 21 and 25 (with dibromo substituents) were equipotent, and more potent than compound 2 (with dichloro substituents), with compound 25 being the most efficacious of all tested compounds.

Novel actions of oxazolidinones: in vitro screening of a triazolyloxazolidinone for anticonvulsant activity.

Objective: To test the hypothesis that a triazolyloxazolidinone (PH084) has anticonvulsant activity by examining its effects on in vitro seizure models in the rat hippocampus.

Materials And Methods: Whole-cell synaptic currents, action potentials and extracellular population spikes (PS) were recorded in the cell body area of rat hippocampal CA1 region in acutely prepared slices. Chemical [picrotoxin (100 µM) and zero magnesium] and electrical seizures were induced and the effect of PH084 (10 µM) was tested on cellular responses, multiple spikes and spontaneous bursting frequencies.

Role of community pharmacists in the prevention and management of the metabolic syndrome in Kuwait.

Background: The metabolic syndrome is a cluster of cardiovascular risk factors and its prevalence is alarmingly high in Kuwait, affecting nearly one third of the adult population. There is lack of information about the role of community pharmacists in the care of patients with the metabolic syndrome.

Objective: To assess the awareness and opinions of community pharmacists about the metabolic syndrome and identify the services they provide for identification, management and monitoring of patients with the metabolic syndrome.

A pharmacokinetic study of a topical anesthetic (EMLA® ) in mouse soft tissue laceration.

The use of topical anesthesia instead of injection of local anesthetics for managing soft tissue lacerations in the emergency situations may be a relief for both patients and surgeons. Topical anesthesia in the form of a cream eutectic mixture of local anesthetics (EMLA®) containing 2.5% lidocaine and 2.

TH-9 (a theophylline derivative) induces long-lasting enhancement in excitatory synaptic transmission in the rat hippocampus that is occluded by frequency-dependent plasticity in vitro.

Dementia, especially Alzheimer's disease, is a rapidly increasing medical condition that presents with enormous challenge for treatment. It is characterized by impairment in memory and cognitive function often accompanied by changes in synaptic transmission and plasticity in relevant brain regions such as the hippocampus. We recently synthesized TH-9, a conjugate racetam-methylxanthine compound and tested if it had potential for enhancing synaptic function and possibly, plasticity, by examining its effect on hippocampal fast excitatory synaptic transmission and plasticity.

Anticonvulsant and related neuropharmacological effects of the whole plant extract of Synedrella nodiflora (L.) Gaertn (Asteraceae).

Purpose: The plant Synedrella nodiflora (L) Gaertn is traditionally used by some Ghanaian communities to treat epilepsy. To determine if this use has merit, we studied the anticonvulsant and other neuropharmacological effects of a hydro-ethanolic extract of the whole plant using murine models.

Materials And Methods: The anticonvulsant effect of the extract (10-1000 mg/kg) was tested on the pentylenetetrazole-, picrotoxin-, and pilocarpine-induced seizure models and PTZ-kindling in mice/rats.

Cocaine sensitization does not alter SP effects on locomotion or excitatory synaptic transmission in the NAc of rats.

Substance P (SP) and cocaine employ similar mechanisms to modify excitatory synaptic transmission in the nucleus accumbens (NAc), a region implicated in substance abuse. Here we explored, using NAc slices, whether SP effects on these synaptic responses were altered in rats that have been sensitized to cocaine and whether SP could mimic cocaine in triggering increased locomotion in sensitized rats. Intraperitoneal (IP) injection of naïve rats with cocaine (15 mg/kg) caused increased locomotion by 408.

Anti-tussive and bronchodilator mechanisms of action for the enaminone E121.

Aims: In this study, we investigated whether the enaminone, E121, has anti-tussive effects in a guinea pig model of cough, and if so, whether this effect is mediated via a central or peripheral site of action. We also assessed whether E121 has bronchodilator effects and the molecular mechanisms underlying any anti-tussive and/or bronchodilator effects.

Main Methods: Whole body plethysmography was used to assess both cough and airway obstruction.

In vitro electrophysiological investigations of the acute effects of linezolid and novel oxazolidinones on central nervous system neurons.

Oxazolidinones are a novel class of antibacterial agents with demonstrated activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and enterococci. Prolonged clinical use of linezolid, the prototypical oxazolidinone, results in peripheral, central and optic neuropathies. The cellular mechanism by which it may alter neuronal function to produce these effects is not known.

Selenium as a chemoprotective anti-cancer agent: reality or wishful thinking?

It is generally accepted that selenium (Se) plays an important role in maintaining equilibrium of a healthy organism. It also participates in processes related to carcinogenesis such as inhibition of tumor formation and regression. Scientific data accumulated so far using experimental animal models and from clinical studies devoted to investigating the effects of Se confirm strong relationship or correlation between Se supplementation and tumor frequency of prostate, lungs, liver and colon.

Substance P and cocaine employ convergent mechanisms to depress excitatory synaptic transmission in the rat nucleus accumbens in vitro.

Substance P (SP) has been reported to produce effects on excitatory synaptic transmission in the nucleus accumbens (NAc) that are similar to those induced by cocaine. To address the question of whether SP serves as an endogenous mediator producing cocaine-like effects that are known to be D1-receptor-mediated, we tested the hypothesis that the effects of SP and cocaine on excitatory postsynaptic currents (EPSCs) in the NAc occlude one another. We report here that SP and SP(5-11) actions occlude the effect of cocaine and vice versa.

Norepinephrine and E139 interactions on epileptiform activity in the rat hippocampus in vitro.

Objectives: We tested if E139, an anticonvulsant enaminone, interacts with norepinephrine (NE) to suppress population responses and chemically induced in vitro seizures in the rat hippocampus.

Materials And Methods: Evoked field population spikes (PS) were recorded in the hippocampal CA1 area, and in vitro seizures were generated chemically using the zero Mg(2+) model.

Results: Low concentrations of E139 (or=100 microM) enhanced them.

Synthesis and structure-activity relationship studies of theophylline analogs on population responses in the rat hippocampus in vitro.

We synthesized several theophylline analogs and tested the hypothesis that these compounds may be nootropic or cognitive enhancers by examining their effects on evoked population spikes recorded extracellularly in the CA1 region of the rat hippocampus. Whereas the length of the carbon chain on N7 had no effect, different size of the terminal lactam ring strongly influenced neuroactivity. Our results suggest that hexahydroazepin-2-one analogs have potential for further development as cognitive enhancers.

Anticonvulsant enaminone E139 suppresses epileptiform activity in rat hippocampal slices.

Some enaminones are reported to have in vivo anticonvulsant activity. We asked if methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), one of such enaminones produced in vitro effects that may underlie or explain these in vivo anticonvulsant actions by testing if E139 suppressed in vitro seizures. In vitro seizures were generated chemically in hippocampal slices using picrotoxin and zero Mg(2+) buffer and electrically by high frequency stimulation (HFS).

Enaminones: Exploring additional therapeutic activities.

Enaminones, enamines of beta-dicarbonyl compounds, have been known for many years. Their early use has been relegated to serving as synthetic intermediates in organic synthesis and of late, in pharmaceutical development. Recently, the therapeutic potential of these entities has been realized.