The involvement of opioidergic and noradrenergic mechanisms in nefopam antinociception.

Nefopam is a clinically effective analgesic agent used to control mild to moderate pain, whose mechanism of action is unknown. We have investigated the antinociceptive activity of nefopam in the mouse abdominal constriction assay and tail immersion test (48 degrees C). Nefopam was found to possess a high degree of potency against acetic acid-induced visceral nociception (ED50 2.

The selection and design of topical and transdermal agents: a review.

One of the major problems in topical and transdermal drug delivery is the efficiency of the barrier property of the stratum corneum. Topical and transdermal agents were often originally designed as drugs to be given orally. In this paper a mechanistic evaluation of skin penetration shows that topical and transdermal drugs should be designed using different strategies.

The involvement of the opioidergic system in the antinociceptive mechanism of action of antidepressant compounds.

1. Debate exists as to the nature of antidepressant-induced antinociception. It is unclear whether antidepressants are inherently antinociceptive, are able to potentiate opioid antinociception or both.

PDE4 inhibition and a corticosteroid in chronically antigen exposed conscious guinea-pigs.

Background: The physiological and pharmacological consequences of repeated aero-allergen challenge have not been previously characterized in conscious, sensitized guinea-pigs.

Objectives: This study was undertaken to compare the effects of two anti-inflammatory compounds, dexamethasone and Ro 20- 1724, on an acute and chronic airway inflammation, in terms of airway function, reactivity and leucocyte infiltration.

Methods: Sensitized guinea-pigs received eight saline or ovalbumin (OvA) inhalation exposures over 4 weeks and either vehicle, the type 4 PDE inhibitor, Ro 20-1724 (3 mgkg(-1)), or dexamethasone (1.

Intramembrane molecular dipoles affect the membrane insertion and folding of a model amphiphilic peptide.

The relationship between the dipole potential and the interaction of the mitochondrial amphipathic signal sequence known as p25 with model membranes has been studied using 1-(3-sulfonatopropyl)-4-[beta[2-(di-n-octyl-amino)-6-naphthyl]viny l] pyridinium betaine (di-8-ANEPPS) as a fluorescent probe. The dipole potential of phosphatidylcholine membranes was modified by incorporating into the bilayer the sterols phloretin and 6-ketocholestanol (KC), which decrease and increase the dipole potential, respectively. The results derived from the application of a dual-wavelength ratiometric fluorescence method for following the variation of the membrane dipole potential have shown that when p25 inserts into the lipidic bilayer, a decrease in the dipole potential takes place.

Absorption of materials by or through the living skin.

Synopsis The skin comes into contact with a large range of materials either deliberately or inadvertently. It should be possible to predict the exact transport rates of these materials through the skin as a function of the physicochemical properties of the different compounds. With this sort of knowledge it is possible to predict the exact disposition of compounds and use this in the formulation of new products both in the pharmaceutical and cosmetic field.

The Thermodynamics of Partitioning of Phenothiazines between Phosphate Buffer and the Lipid Phases of Cyclohexane, n-Octanol and DMPC Liposomes.

The partitioning of six phenothiazines was determined between phosphate buffer (pH 6.0) and the lipid phases of cyclohexane, n-octanol and dimyristoyl phosphatidylcholine (DMPC). For DMPC liposomes studies were carried out both below and above the phase transition temperature (Tc) of the liposomes.