6-Benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones substituted withibuprofen: synthesis, characterization and evaluation of anti-inflammatory activity.

In this study, the synthesis of 3-[1-(4-(2-methylpropyl)phenyl)ethyl]-1,2,4-triazole-5-thione (2) and its condensed derivatives 6-benzylidenethiazolo[3,2-b]-1,2, 4-triazole-5(6H)-ones (2a-u) are described. The structures of the compounds were elucidated by spectral and elemental analysis. In the pharmacological studies, anti-inflammatory activities of these compounds have been screened. Among the compounds examined, the compounds 2 and 2g possessed the most prominent and consistent activity. In gastric ulceration studies the synthesized compounds were generally found to be safe at a 200 mg/kg dose level.

Synthesis of some novel 3-methyl-6-(2-substituted propanoyl/propyl)-2-benzoxazolinone derivatives and anti-nociceptive activity.

In this study, 12 new 3-methyl-6-(2-substituted aminopropanoyl)-2-benzoxazolinone and 3-methyl-6-(1-hydroxy-2-substituted aminopropyl)-2-benzoxazolinone derivatives have been prepared. Their structures have been elucidated by IR, 1H NMR spectra and by elementary analysis. The anti-nociceptive activity of these compounds has been investigated by using a modified Koster test. It was found that most compounds are capable of inducing anti-nociception in animals.

5-methyl-8-N-substituted-thiocarbamoyl-7,8-diazabicyclo[4.3.0] non-6-enes: evaluation as BSAO inhibitors and pharmacological activity screening.

In this study a series of 5-methyl-8-N-substituted-thiocarbamoyl-7,8-diazabicyclo[4.3.0] non-6-enes derivatives previously synthesized and separated to their stereoisomers, were evaluated as BSAO inhibitors and screened pharmacologically for antidepressant activity, effect on anxiety and experimental parkinsonism by in vivo tests. The title compounds caused 30-40% inhibition irrespective of geometric isomerism as well as nature of substituent. On the other hand, their open chain derivative NBE (4-ethyl, p-methoxybenzylidenthiosemicarbazide) showed a marked enzyme inhibition and antidepressant effect. While the other group was inactive as antidepressant effect, these compounds have shown diastereoselective antitremor activity by inhibiting the tremors induced by oxotremorin in mice pretreated with dopaminergic antagonist haloperidol. The title compounds constitutes a new class of BSAO inhibitors and may serve as usefull leads for further investigation as specific BSAO inhibitors, antiparkinson, antidepressant and anticholinergic agents.

Analgesic activity of acylated 2-benzoxazolinone derivatives.

Ten new benzoxazolinone derivatives having a disubstituted benzoyl group at the six position of the ring were synthesized by reacting 2-benzoxazolinone with aromatic carboxylic acids in the presence of polyphosphoric acid. The structure of the compounds were elucidated by IR, 1H NMR, MS and elemental analysis. Analgesic activity was evaluated by a modified Koster test. Seven compounds showed analgesic activities higher than that of acetylsalicylic acid.

Interaction of rat lung SSAO with the novel 1-N-substituted thiocarbamoyl-3-substituted phenyl-5-(2-pyrolyl)-2-pyrazoline derivatives.

Interactions of twelve new synthesized 1-N-substituted thiocarbamoyl-3-substituted phenyl-5-pyrolyl-2-pyrazoline derivatives with rat lung semicarbazide-sensitive amine oxidase (SSAO) were assessed. Pyrazoline derivatives were synthesized according to previous methods and SSAO was purified from the crude microsomal fractions of rat lung.Three compounds (3e, 3f, 3k) with a p-methoxy group at the phenyl ring inhibited rat lung SSAO non-competitively and irreversibly, and showed higher affinity towards SSAO when expressed in terms of IC(50) for SSAO/Monoamine oxidase B (MAO-B). Since these novel pyrazoline derivatives have been found to act as suicide inhibitors of SSAO, the semicarbazide group in these molecules may be responsible for the SSAO inhibitory action. It is suggested that these compounds cannot enter the first small active site cavity of SSAO and may interact tightly with another binding site or with some other reactive groups present in the molecule. Compound 3e showed the highest inhibitory activity on rat lung SSAO. The novel pyrazoline derivatives may be used to discriminate between Cu- and FAD-containing amine oxidases and may have promising features as anti-Parkinson agents if the SSAO-inhibitory effects can be supported by in vivo studies.

Water and electrolyte content of rabbit brain after opening the blood-brain barrier by acute hypertension.

Changes in water and electrolyte content of the brain and edema formation after acute, drug-induced hypertension were studied in albino rabbits. Blood-brain and blood-cerebrospinal fluid (CSF) barriers opened to Evans blue-albumin when systemic blood pressure was elevated abruptly to more than 160 mm Hg by i.v. injection of Aramin. No statistically significant changes in sodium and potassium content of brain, muscle, and CSF were observed. Measurable brain edema did not develop. The results suggest that short-lasting hypertensive barrier opening does not cause brain edema, but may enhance a tendency for brain edema.

Changes in cyclic nucleotides during the calcium paradox in the isolated rat heart.

Reperfusion of hearts with a Ca2+-containing medium after a perfusion period in Ca2+-free medium results in irreversible cell damage (calcium paradox). In this investigation we have studied coronary flow and cyclic AMP and cyclic GMP levels after several periods of Ca2+-free perfusion in isolated rat hearts. We also investigated the effects of papaverine (Pap), noradrenaline (NA), acetylcholine (ACh) and absence of inorganic phosphate during Ca2+-free perfusion on coronary flow (CF) and cyclic nucleotide levels. Inability of the heart to recover contractile activity with development of contracture during the reperfusion period was accepted as indicative of the calcium paradox. Ca2+-free perfusion alone and NA and absence of inorganic phosphate during the Ca2+-free perfusion period increased CF, whereas Pap and ACh decreased it. However, only Ca2+-free perfusion and NA elevated cyclic AMP. On the other hand, Pap and ACh increased cyclic GMP (with a transient rise of cyclic AMP in Pap infusion), and absence of inorganic phosphate decreased both cyclic AMP and cyclic GMP. Pap, ACh and absence of phosphate prevented the calcium paradox. Our study suggests that increased cyclic AMP during the Ca2+-free perfusion may contribute, with the other factors, to the occurrence of the calcium paradox.

Novel antiinflammatory analgesics: 3-(2-/4-pyridylethyl)-benzoxazolinone and oxazolo[4,5-b]pyridin-2-one derivatives.

Twenty-two new 3-[2-(2-and/or 4-pyridyl)ethyl]benzoxazolinone and oxazolo[4,5-b]pyridin-2-one derivatives have been synthesized by reacting 2- and/or 4-vinylpyridine and appropriate benzoxazolinones and oxazolo[4,5-b]pyridine-2-one. Their chemical structures have been proven by IR. 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis. The analgesic activities of these compounds were investigated by a modified Koster's Test. Test results revealed that, at 100 mg/kg dose level, most of the compounds showed significant analgesic activities when compared to aspirin. Therefore the compounds were screened for their antiinflammatory activities using the carrageenan hind paw edema test. Compounds 1, 7, 10, 11, 12, 13, 15, 18, 20, 21 were found more active than indomethacine. In gastric ulceration studies gastrointestinal bleeding was not observed at 100 mg/kg dose level in compounds 1 and 2.

Movement-related cortical potentials: their relationship to the laterality, complexity and learning of a movement.

Movement-related cortical potentials (MRCPs) to self-paced unilateral movements of different laterality, complexity and practice level were recorded from 14 healthy subjects using the EMG onset as the trigger. The amplitudes at certain time points and slopes of linear regression lines fitted to 3 main shifts have been evaluated. In the early phase of MRCP the potential and slope values were symmetrically distributed around the midline maximum, which indicates that this part of MRCP can not originate from the primary motor area, which is in a contralateral relation with the movement, but from secondary motor areas (SMA and premotor areas). The changes in the voltage levels and slopes of this phase due to the changes in laterality, complexity and practice level of the movement show the relation of this activity with the abstract characteristics of the movement. The decrease of voltages and slope values in the later phases of MRCP in the complex task, which is replaced by higher voltages and slopes after a certain learning period was evaluated as a result of inhibition of associative movements via reafferent feedback signals occurring often in the first stages of learning period.

Synthesis of some new pyridyl-ethylated benzoxazolinones with analgesic and anti-inflammatory activities.

Twelve new 3-[2-(2- and/or 4-pyridyl)ethyl]benzoxazolinone derivatives have been synthesized by reacting 2- and/or 4-vinylpyridine and appropriate benzoxazolinones. Their chemical structures have been proven by IR, 1H-NMR and elemental analysis. Analgesic activities of these compounds were investigated by a modified Koster and constant temperature hot-plate test. Test results revealed that most of the compounds at 100 mg/kg dose level showed significant analgesic activities when compared to acetylsalicylic acid and morphine. Therefore the compounds were screened for their anti-inflammatory activities using the carrageenan hind paw edema test. Compounds 3-8 were found more active than indometacin. In gastric ulceration studies, any of the compounds showed no gastrointestinal bleeding at 100 mg/kg dose level.