Analgesic and Psychotropic Effects of a New Bradykinin Antagonist.

A bradykinin B receptors antagonist PAV-0056, an 1,4-benzodiazepin-2-one derivative, intragastrically administrated to mice at doses of 0.1 and 1 mg/kg causes analgesia in the "formalin test" not inferior to that of diclofenac sodium (10 mg/kg) and tramadol (20 mg/kg). PAV-0056 at doses of 0.

Subdural CMOS optical probe (SCOPe) for bidirectional neural interfacing.

Optical neurotechnologies use light to interface with neurons and can monitor and manipulate neural activity with high spatial-temporal precision over large cortical extents. While there has been significant progress in miniaturizing microscope for head-mounted configurations, these existing devices are still very bulky and could never be fully implanted. Any viable translation of these technologies to human use will require a much more noninvasive, fully implantable form factor.

Analytical Solutions for Simple Turbulent Shear Flows on a Basis of a Generalized Newton's Law.

In the presented article a generalization of Newton's formula for the shear stress in a fluid is carried out by giving it a power-law form. After the introduction of the corresponding strain rate tensor, a generalization is made to the spatial case of flow and the rheological relation is presented in tensor form. Depending on the power value in this rheological ratio, one can come either to a description of a laminar flow regime (in the form of Navier-Stokes equations), or to a description of the flow in turbulent regime.

Activity of 1-aryl-4-(naphthalimidoalkyl) piperazine derivatives against Leishmania major and Leishmania mexicana.

A series of 1-aryl-4-(phthalimidoalkyl) piperazines and 1-aryl-4-(naphthalimidoalkyl) piperazines were retrieved from a proprietary library based on their high structural similarity to haloperidol, an antipsychotic with antiparasitic activity, and assessed as potential antileishmanial scaffolds. Selected compounds were tested for antileishmanial activity against promastigotes of Leishmania major and Leishmania mexicana in dose-response assays. Two of the 1-aryl-4-(naphthalimidoalkyl) piperazines (compounds 10 and 11) were active against promastigotes of both Leishmania species without being toxic to human fibroblasts.

Quantitative determination of new anti-inflammatory drug indomenthyl and its metabolite in rabbit plasma by HPLC-MS/MS.

: Indomenthyl is an innovative anti-inflammatory drug with a high analgesic activity. Indomenthyl releases indomethacin under the influence of neutrophil esterases in the inflammation focus. /: This research is aimed at developing a highly sensitive method for the quantitative determination of indomenthyl and its active metabolite indomethacin in rabbit plasma by HPLC-MS/MS.

Butorphanol induces anxiety-like -behaviour and distress in piglets.

In a previous study that used butorphanol in pigs before castration performed under isoflurane anaesthesia, severe adverse effects were recorded. As in pigs, this has not been reported before, we aimed to investigate the effects of butorphanol in piglets. In this study ten 27 days old piglets were randomly allocated to receive either 0,2 mg/kg butorphanol (group B) or saline 0,9% (control group C) intramuscularly.

Synthesis, Biological Evaluation, and Molecular Modeling of Aza-Crown Ethers.

Synthetic and natural ionophores have been developed to catalyze ion transport and have been shown to exhibit a variety of biological effects. We synthesized 24 aza- and diaza-crown ethers containing adamantyl, adamantylalkyl, aminomethylbenzoyl, and ε-aminocaproyl substituents and analyzed their biological effects in vitro. Ten of the compounds (, -, and ) increased intracellular calcium ([Ca]) in human neutrophils, with the most potent being compound (,'-[2-(1-adamantyl)acetyl]-4,10-diaza-15-crown-5), suggesting that these compounds could alter normal neutrophil [Ca] flux.

Effect of 3-substituted 1,4-benzodiazepin-2-ones on bradykinin-induced smooth muscle contraction.

Biochemical properties of 3-substituted 1,4-benzodiazepine determined by the characteristics of their chemical structure. Influence of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate and amplitudes of isometric smooth muscle contraction in rats was investigated. Compounds MX-1775 and MX-1828 demonstrated the similar inhibition effect on bradykinin-induced contraction of smooth muscle like competitive inhibitor des-arg9-bradykinin-acetate to bradykinin B2-receptors.

Fast optical pH manipulation and imaging.

We describe a complete system for optical pH manipulation and imaging. The system consists of a photoactive Ruthenium complex capable of inducing a change of more than 5 pH units at the nanosecond time scale. A compatible imaging system acquires microscopic pH images at 1200 fps using a nonexpensive commercial digital camera and an LED illumination system.

Synthesis, structure and affinity of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones for CNS central and peripheral benzodiazepine receptors.

A series of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (7-15) was synthesized and their in vitro affinity for both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor (PBR) of rat brain was studied. Racemic mixture of 7-bromo-3-(2-methoxy)ethoxy-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one (13) was separated into enantiomers 14, 15 by chiral HPLC. Absolute configuration of R-enantiomer 15 was determined by the method of X-ray diffraction analysis.

Affinities of gidazepam and its analogs for mitochondrial benzodiazepine receptors.

Mitochondrial benzodiazepine receptors (MBRs) participate in many physiological processes, such as calcium flow regulation, proliferative and respiratory cell functions, mitochondrial steroidogenesis and adaptational reactions to stress. We have found that the selective anxiolytic gidazepam has a higher affinity for CNS MBRs as compared to central benzodiazepine receptors. The ability of gidazepam to bind to MBRs probably underlies a wide spectrum of its pharmacological effects.