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PubMed1983

Synthesis of perhydro-1,4-thiazepines, of expected pharmacological activity. Part III. 4-(2-hydroxyethyl)-perhydro-1,4-thiazepine esters.

New esters, derivatives or the title aminoalcohol, were obtained by three classical methods in the reaction of 4-(2-hydroxyethyl)-perhydro-1,4-thiazepine (HEPT) with chlorides (method a), acid potassium salts (method b), and sodium HEPT salts with acid chlorides (method c). Compounds 3 and 5 have weak spasmolytic properties; 5 in a dose of approx. 50 mg/kg strongly depressed the central nervous system.

Animals↗
PubMed1989

Pharmacological alterations of the activity of afferent fibers innervating hair cells.

To determine whether some of the substances that may be present in hair-cell sensory organs could affect neural activity in afferent fibers, we examined 56 compounds for the ability to alter the discharge rate of afferent fibers innervating hair cells in the lateral line organ of Xenopus laevis, the African clawed frog. These compounds included amino acids, glutamyl dipeptides, standard neurotransmitter candidates, and other constituents of tissues and body fluids. Substances found to be excitatory included some neutral amino acids (alanine, serine, threonine, asparagine, glutamine, and proline), ATP, carnosine, histidine, and barium chloride. Compounds that suppressed discharge included the aromatic amino acids (phenylalanine, tryptophan, and tyrosine), serotonin, and gamma-glutamyl dipeptides. GABA and acidic amino acids (glutamate, aspartate, and cysteine sulfinate) produced a brief excitation followed by a suppression of discharge rate. Several of these substances were active at sufficiently low concentrations that their presence in body fluids may affect afferent fiber discharge rate under normal or pathological conditions.

Amino Acids↗
PubMed1978

Cholinergic receptor mechanisms in amphibian vasoconstrictor responses.

The four choline esters, namely acetylcholine, carbachol, methacholine and bethanechol, produced constriction of frog's perfused systemic blood vessels, acetylcholine and carbachol being more potent than methacholine and bethanechol. Pentolinium and dihydroergotamine, in submaximal receptor-blocking doses, also produced a uniform partial inhibition of all choline esters and other agonists including the direct-acting barium chloride. On the other hand atropine markedly inhibited the responses of the four choline esters without affecting the adrenaline and barium responses. Compound AHR-602, a specific ganglionic muscarinic excitatory receptor stimulant, did not produce any effect in these experiments. Eserine in higher doses produced slight vasoconstriction and markedly potentiated acetylcholine responses, but it inhibited partially those of the other three choline esters without significantly affecting adrenaline and barium responses. The results provide strong evidence in favor of involvement of the postganglionic muscarinic receptors only in vasoconstriction after choline esters. There seems to be a considerable nonspecific inhibitory activity in ganglionic and alpha-adrenergic blockers in their submaximal receptor-blocking doses. It may be that in frog the adrenergic and nicotinic receptors are not as well differentiated as muscarinic receptors are. The ganglionic muscarinic receptors also seem to be absent in the frog.

Acetylcholine↗
PubMed1984

No correlation exists between antidepressant activity and the ability of 5-HT uptake inhibitors to interact with 5-HT receptors of the rat stomach fundus strip.

Several 5-HT uptake inhibitors, established and potential antidepressant drugs, were tested for their ability to counteract contractions of the rat isolated stomach fundus strip induced by 5-HT and BaCl2. Of 12 inhibitors tested, only doxepine, amitriptyline, clomipramine, imipramine, Ro 11-2465 (cyan-imipramine), citalopram and fluvoxamine antagonized the contraction induced by 10(-6) M 5-HT with IC50 values below 10(-4) M. Amitriptyline, doxepine and cyproheptadine, at concentrations inhibiting the effect of 5-HT, did not antagonize the strip contractions induced by 3 X 10(-3) M BaCl2, while the remaining compounds that antagonized 5-HT-induced contractions, also antagonized--with at least a similar potency--the contractions induced by BaCl2. From among antidepressant compounds investigated, only doxepine and amitriptyline may be regarded as antagonists of the 5-HT receptor in the rat stomach strip.

Animals↗
PubMed1984

Antagonistic activity of verapamil and diltiazem against different intestinal smooth muscle stimuli.

Investigations in the isolated guinea-pig ileum have shown an almost equal inhibitory activity of verapamil and diltiazem against contractions elicited by histamine, 5-HT, acetylcholine and BaCl2. While dicycloverine (dicyclomine) has a specific anticholinergic action, no specific action against any of the stimulating compounds including BaCl2 could be differentiated. Verapamil and diltiazem seem to have good oral "unspecific" spasmolytic properties, which might be of clinical value. The results let us assume that the site of the calcium antagonists action of verapamil and diltiazem in the intestinal smooth muscle could be at a common entrance of Ca2+ released by receptor operating compounds and of Ba2+ into the cell or at structures from which BaCl2 as well as the other agonists release Ca2+.

Acetylcholine↗
PubMed2000

Afferent loop syndrome: the role of Tc-99m mebrofenin hepatobiliary scintigraphy.

Afferent loop syndrome is caused by intermittent mechanical obstruction of the afferent loop of a gastrojejunostomy and may present early as an acute type or late as a chronic type. The authors describe two patients who were examined for a history of bilious vomiting after gastrojejunostomy, and who were thought to have afferent loop syndrome (chronic type) based on clinical findings. Results of routine investigations, such as upper gastrointestinal endoscopy, and ultrasonography were inconclusive. Findings from the barium meal follow-through studies were normal in the first patient and revealed a dilated duodenum in the second patient. Tc-99m bromotriethyl-iminodiacetic acid has been used to identify afferent loop obstruction as represented in these studies.

Adult↗
PubMed1988

Synthesis and pharmacological characterization of a series of leukotriene analogues with antagonist and agonist activities.

The synthesis and biological characterization of a series of novel leukotriene antagonists and agonists are reported. All of these compounds are derivatives of (5S,6R,7Z)-5-hydroxy-6-mercapto-9-phenyl-7-nonenoic acid. One of the more potent compounds is (5S,6R,7Z)-6-[[(4-carboxy-2-methoxyphenyl)methyl]thio]-5-hydroxy-9 -(4- heptylphenyl)-7-nonenoic acid (3f). In vitro evaluation of this compound on guinea pig trachea revealed that it is a competitive antagonist of LTD4 and LTE4 with pKB values of 6.4 and 5.8, respectively. On guinea pig ileum, the pKB values obtained for it with LTD4 and E4 were both 7.2. The selectivity of 3f was shown by its lack of effect on carbachol, histamine, and barium chloride concentration-response curves in guinea pig trachea.

Animals↗
PubMed1992

Quantification of the degradation products of sevoflurane in two CO2 absorbants during low-flow anesthesia in surgical patients.

Sevoflurane, a new inhalational anesthetic agent has been shown to produce degradation products upon interaction with CO2 absorbants. Quantification of these sevoflurane degradation products during low-flow or closed circuit anesthesia in patients has not been well evaluated. The production of sevoflurane degradation products was evaluated using a low-flow anesthetic technique in patients receiving sevoflurane anesthesia in excess of 3 h. Sevoflurane anesthesia was administered to 16 patients using a circle absorption system with O2 flow of 500 ml/min and average N2O flow of 273 ml/min. Preoperative and postoperative hepatic and renal function studies were performed. Gas samples were obtained from the inhalation and exhalation limbs of the anesthetic circuit for degradation product analysis and analyzed by gas chromatography/mass spectrometry for four degradation products. The first eight patients received sevoflurane anesthesia using soda lime, and the following eight patients received anesthesia using baralyme as the CO2 absorbant. CO2 absorbant temperatures were measured during anesthesia. Of the degradation products analyzed, only one compound [fluoromethyl-2, 2-difluoro-1-(trifluoromethyl) vinyl ether], designated compound A, was detectable. Concentrations of compound A increased during the first 4 h of anesthesia with soda lime and baralyme and declined between 4 and 5 h when baralyme was used. Mean maximum inhalation concentration of compound A using baralyme was 20.28 +/- 8.6 ppm (mean +/- SEM) compared to 8.16 +/- 2.67 ppm obtained with soda lime, a difference that did not reach statistical significance. A single patient achieved a maximal concentration of 60.78 ppm during low-flow anesthesia with baralyme. Exhalation concentrations of compound A were less than inhalation concentrations, suggesting patient uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1997

Dehydration of Baralyme increases compound A resulting from sevoflurane degradation in a standard anesthetic circuit used to anesthetize swine.

UNLABELLED: In a model anesthetic circuit, dehydration of Baralyme brand carbon dioxide absorbent increases degradation of sevoflurane to CF2=C(CF3)OCH2F, a nephrotoxic vinyl ether called Compound A. In the present study, we quantified this increase using "conditioned" Baralyme in a circle absorbent system to deliver sevoflurane anesthesia to swine. Mimicking continuing oxygen delivery for 2 days after completion of an anesthetic, we directed a conditioning fresh gas flow of 5 L/min retrograde through fresh absorbent in situ in a standard absorbent system for 40 h. The conditioned absorbent was subsequently used (without mixing of the granules) in a standard anesthetic circuit to deliver sevoflurane to swine weighing 78 +/- 2 kg. The initial inflow rate of fresh gas flow was set at 10 L/min with the vaporizer at 8% to achieve the target end-tidal concentration of 3.0%-3.2% sevoflurane in approximately 20 min. The flow was later decreased to 2 L/min, and the vaporizer concentration was decreased to sustain the 3.0%-3.2% value for a total of 2 h (three pigs) or 4 h (eight pigs). Inspired Compound A increased over the first 30 +/- 60 min to a peak concentration of 357 +/- 49 ppm (mean +/- SD), slowly decreasing thereafter to 74 +/- 6 ppm at 4 h. The average concentration over 2 h was 208 +/- 25 ppm, and the average concentration over 4 h was 153 +/- 19 ppm. Pigs were killed 1 or 4 days after anesthesia. The kidneys from pigs anesthetized for both 2 h and 4 h showed mild inflammation but little or no tubular necrosis. These results suggest that dehydration of Baralyme may produce concentrations of Compound A that would have nephrotoxic effects in humans in a shorter time than would be the case with normally hydrated Baralyme. IMPLICATIONS: The vapor known as Compound A can injure the kidney. Dehydration of Baralyme, a standard absorbent of carbon dioxide in inhaled anesthetic delivery systems, can cause a 5- to 10-fold increase in Compound A concentrations produced from the inhaled anesthetic, sevoflurane, given at anesthetizing concentrations in a conventional anesthetic system.

Anesthesia, Closed-Circuit↗
PubMedDate not supplied

[The anti-arrhythmia activity of new dicyclohexylamide derivatives of N-substituted alpha-aminocarboxylic acids].

Experiments on arrhythmia models showed a high antiarrhythmic activity of new derivatives of dicyclohexylamides of N-replaced alpha-aminocarbonic acids. The new compounds surpassed in intensity and duration of the antiarrhythmic effect the standard agents with classes I and III antiarrhythmic activity. In doing so they raise myocardial electrical stability and prevent sudden development of ventricular fibrillation. According to the mechanism of the antiarrhythmic activity, the new compounds may be related to antiarrhythmic agents possessing the properties of classes I and III.

Aconitine↗
PubMed1989

Interaction of potassium channel openers and blockers in canine atrial muscle.

1. The possibility that the interaction between potassium channel openers, e.g. cromakalim, pinacidil and nicorandil, and some potassium channel blockers involves a common site was investigated in canine atrial muscle. 2. Cromakalim, pinacidil and nicorandil produced a negative inotropic effect, their pD2 (-log EC50) values being 6.11 +/- 0.07, 5.37 +/- 0.09 and 4.55 +/- 0.07, respectively. 3. The potassium channel blockers, tetraethylammonium (TEA), tetrabutylammonium (TBA), 3,4-diaminopyridine (DAP), CsCl and BaCl2 all produced a positive inotropic effect. 4. The concentration-effect curves for the negative inotropic actions of pinacidil were shifted in a parallel way to the right by low concentrations of TEA, TBA or BaCl2. Maximum responses to pinacidil were depressed by higher concentrations of the blockers. An analysis of the non-competitive antagonism by TEA yielded pKA (-log KA) values of 4.00-4.05 for pinacidil. 5. The concentration-effect curves for cromakalim and nicorandil were shifted by TEA similarly to those for pinacidil, and a similar analysis yielded pKA values of 4.47-4.68 for cromakalim and 3.47-3.74 for nicorandil. 6. The KA values of cromakalim, pinacidil and nicorandil were about 10-30 times greater than their EC50 values, indicating that there are non-linear stimulus-effect relationships between the binding of the three potassium channel openers to their binding sites at potassium channels and their negative inotropic effects. 7. The dissociation constants for TEA could also be estimated from pA2 and pKB values for antagonizing competitively and non-competitively the negative inotropic effects of the three potassium channel openers; they were 3.47-3.89, and did not differ between the potassium channel openers. 8. The concentration-effect curves for the three potassium channel openers were not affected by DAP or CsCl. 9. These results suggest the following: (i) quaternary ammonium compounds like TEA and TBA antagonize the negative inotropic effect of cromakalim, pinacidil and nicorandil by binding to potassium channels, thus preventing binding of the channel openers to the same sites or closely related sites in canine right atrial muscles.

Animals↗
PubMedDate not supplied

Derivatives of 2-mercaptobenzenesulphonamide. XVIII. Syntheses and cardiovascular effects of some S- and S,N-substituted 4-chloro-2-mercapto-5-methyl-N-(5-amino-1,2,4-triazol-3-yl) benzenesulphonamide derivatives.

The syntheses of salts [III, IV] and amides [V, V.HCl] of 2-[5-chloro-4-methyl-2-[(5-amino-s-triazol-3-yl)aminosulphonyl+ ++] phenylthio] alkanoic acids, as well as 5-amino-2-[2-(2,4-dimethylpiperidino) ethyl]-3-[4-chloro-2-[2-(2,6-dimethylpiperidino) ethylthio]-5-methylbenzenesulphonylimino]-1-methyl-delta 4-1,2,4-triazoline dihydrochloride [X] and 5-(amino-, 4-chloroanilino- or 3,4,5-trimethoxyanilino)-1,2-di[2-(2,6-dimethylpiperidino) ethyl]-3-(4-chloro-2-[2-(2,6-dimethylpiperidino) ethylthio]-5-methylbenzenesulphonylimino)-delta 4-1,2,4-triazoline trihydrochlorides [XI-XIII] are described. The results of preliminary pharmacological examinations such as acute toxicity and influence on circulatory system of compounds III, IV, V.HCl and X-XIII are presented. The antiarrhythmic effect of the most active [XI] was stronger or comparable to the reference drugs quinidine and procainamide.

4-Chloromercuribenzenesulfonate↗
PubMed2002

Alkaloids, amides and antispasmodic activity of Zanthoxylum hyemale.

Two quinoline alkaloids, (-)-R-geilbalansine (1) and hyemaline (2), as well as aromatic amide, N-[2-(3,4-dimethoxyphenyl)-2-methoxyethyl)-2-methoxyethyl]benzamide (O-methylbalsamide) (3), were isolated as new natural products from the stem barks of Zanthoxylum hyemale, together with seven known compounds. Their structures were determined on the basis of spectroscopic data (IR, (1)H- and (13)C-NMR, MS). In addition, the antispasmodic activity of the crude extract of Z. hyemale and three other more abundant isolated compounds (4, 5 and 10) were studied in two different antispasmodic test models on isolated rat ileum and only the crude ethanolic extract presented antispasmodic activity.

Acetylcholine↗
PubMed2003

Effect of different solution flow rates on analyte ion signals in nano-ESI MS, or: when does ESI turn into nano-ESI?

In nano-ESI MS, the qualitative and quantitative characteristics of mass spectra vary considerably upon the use of different spraying conditions, i.e., aperture of the spraying needle and the voltage applied. The major parameters affected by the aperture size is the liquid flow rate which determines the initial droplet size and the current emitted upon the spray process, as described by different models of the ESI process. In the present study, the effect of flow rate on ion signals was studied systematically using mixtures of compounds with different physicochemical properties (i.e., detergent/oligosaccharide and oligosaccharide/peptide). For these model systems, the functional dependence of certain analyte-ion ratios upon the flow rate can be correlated to changes in analyte partition during droplet fission prior to ion release. Analyte suppression is practically absent at minimal flow rates below 20 nL/min.

Barium Compounds↗
PubMed2002

Comparison of Amsorb, sodalime, and Baralyme degradation of volatile anesthetics and formation of carbon monoxide and compound a in swine in vivo.

BACKGROUND: Consequences of volatile anesthetic degradation by carbon dioxide absorbents that contain strong base include formation of compound A from sevoflurane, formation of carbon monoxide (CO) and CO toxicity from desflurane, enflurane and isoflurane, delayed inhalation induction, and increased anesthetic costs. Amsorb (Armstrong Ltd., Coleraine, Northern Ireland) is a new absorbent that does not contain strong base and does not form CO or compound A in vitro. This investigation compared Amsorb, Baralyme (Chemetron Medical Division, Allied Healthcare Products, St. Louis, MO), and sodalime effects on CO (from desflurane and isoflurane) and compound A formation, carboxyhemoglobin (COHb) concentrations, and anesthetic degradation in a clinically relevant porcine in vivo model. METHODS: Pigs were anesthetized with desflurane, isoflurane, or sevoflurane, using fresh or partially dehydrated Amsorb, Baralyme, and new and old formulations of sodalime. Anesthetic concentrations in the fresh (preabsorber), inspired (postabsorber), and end-tidal gas were measured, as were inspired CO and compound A concentrations and blood oxyhemoglobin and COHb concentrations. RESULTS: For desflurane and isoflurane, the order of inspired CO and COHb formation was dehydrated Baralyme >> soda-lime > Amsorb. For desflurane and Baralyme, peak CO was 9,700 +/- 5,100 parts per million (ppm), and the increase in COHb was 37 +/- 14%. CO and COHb increases were undetectable with Amsorb. Oxyhemoglobin desaturation occurred with desflurane and Baralyme but not Amsorb or sodalime. The gap between inspired and end-tidal desflurane and isoflurane did not differ between the various dehydrated absorbents. Neither fresh nor dehydrated Amsorb caused compound A formation from sevoflurane. In contrast, Baralyme and sodalime caused 20-40 ppm compound A. The gap between inspired and end-tidal sevoflurane did not differ between fresh absorbents, but was Amsorb < sodalime < Baralyme with dehydrated absorbents. CONCLUSION: Amsorb caused minimal if any CO formation, minimal compound A formation regardless of absorbent hydration, and the least amount of sevoflurane degradation. An absorbent like Amsorb, which does not contain strong base or cause anesthetic degradation and formation of toxic products, may have benefit with respect to patient safety, inhalation induction, and anesthetic consumption (cost).

Absorption↗
PubMed1994

Long-duration, low-flow sevoflurane anesthesia using two carbon dioxide absorbents. Quantification of degradation products in the circuit.

BACKGROUND: Sevoflurane reacts with soda lime, generating degradation products. The concentrations of sevoflurane degradation products in a low-flow circuit have been reported for anesthesia times of less than 5 h. In this study, sevoflurane degradation products generated during low-flow anesthesia exceeding 10 h were examined. METHODS: Sixteen patients received sevoflurane anesthesia with a fresh gas flow rate of 11/min. In eight patients, soda lime was used as the CO2 absorbent; in the other eight patients, Baralyme was used. During anesthesia, the concentrations of degradation products in the circuit, the temperature of the CO2 absorbent, inspired and end-tidal sevoflurane concentrations, and the volume of CO2 eliminated by the patient were measured. Gas was sampled from the inspiratory limb of the circuit and analyzed by gas chromatography. RESULTS: Two degradation products, CF2 = C(CF3)-O-CH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B), were detected. In the soda lime group, the individual maximum concentration of compound A was 23.6 +/- 2.9 (12.0-37.4) ppm. In the Baralyme group, the concentration was 32.0 +/- 2.3 (23.5-41.3) ppm. The individual maximum concentration of compound A in the Baralyme group was significant higher than A in the Baralyme group was significant higher than that in the soda lime group. Compound B was detected in two patients, reaching a maximum concentration of 0.2 ppm. The end-tidal sevoflurane concentration, temperature of the CO2 absorbent, and volume of CO2 eliminated by the patient were the same in both groups. CONCLUSIONS: The degradation products detected were at low concentrations in long-duration, low-flow anesthesia with sevoflurane. Baralyme produced higher concentrations of degradation products than soda lime.

Adsorption↗
PubMed2005

Synthesis of new visible light active photocatalysts of Ba(In(1/3)Pb(1/3)M'(1/3))O3 (M' = Nb, Ta): a band gap engineering strategy based on electronegativity of a metal component.

We have synthesized new, efficient, visible light active photocatalysts through the incorporation of highly electronegative non-transition metal Pb or Sn ions into the perovskite lattice of Ba(In(1/3)Pb(1/3)M'(1/3))O3 (M = Sn, Pb; M' = Nb, Ta). X-ray diffraction, X-ray absorption spectroscopic, and energy dispersive spectroscopic microprobe analyses reveal that tetravalent Pb or Sn ions exist in the B-site of the perovskite lattice, along with In and Nb/Ta ions. According to diffuse UV-vis spectroscopic analysis, the Pb-containing quaternary metal oxides Ba(In(1/3)Pb(1/3)M'(1/3))O3 possess a much narrower band gap (E(g) approximately 1.48-1.50 eV) when compared to the ternary oxides Ba(In(1/2)M'(1/2))O3 (E(g) approximately 2.97-3.30 eV) and the Sn-containing Ba(In(1/3)Sn(1/3)M'(1/3))O3 derivatives (E(g) approximately 2.85-3.00 eV). Such a variation of band gap energy upon the substitution is attributable to the broadening of the conduction band caused by the dissimilar electronegativities of the B-site cations. In contrast to the ternary or the Sn-substituted quaternary compounds showing photocatalytic activity under UV-vis irradiation, the Ba(In(1/3)Pb(1/3)M'(1/3))O3 compounds induce an efficient photodegradation of 4-chlorophenol under visible light irradiation (lambda > 420 nm). The present results highlight that the substitution of electronegative non-transition metal cations can provide a very powerful way of developing efficient visible light harvesting photocatalysts through tuning of the band structure of a semiconductive metal oxide.

Adsorption↗
PubMed1987

Changes in duodenal contractility induced by "calcium antagonists" with different modes of action.

The inhibitory action of nifedipine, verapamil, diltiazem and trifluoperazine has been examined on isolated duodenum from rats and rabbits. On rabbit duodenum Ca2+ antagonists caused a reduction of the spontaneous motility in very low concentrations (10(-12)-10(-6)M). On rat duodenum Ca2+ antagonists inhibited the contractile response to BaCl2, CaCl2 and to field stimulation, nifedipine being the most potent compound (threshold concentration down to 10(-12)M). The above results indicated that Ca2+ antagonists can markedly alter the duodenal motility, both basal and drug-stimulated. The high potency of nifedipine and the selective antagonism by Bay K 8644 against nifedipine suggest the presence of a specific receptor for the dihydropyridines (DHP receptor) in the duodenum.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗