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At least 793 records · Page 44Linked to original sources

PubMed1998

Vasorelaxant effects of SCA40 (a phosphodiesterase III inhibitor) in pulmonary vascular preparations in rats.

1. The novel phosphodiesterase (PDE) inhibitor SCA40 (6-bromo-8(methylamino)imidazo[1,2-a]pyrazine-2-carbonitrile) was examined for its vasorelaxant activity on isolated pulmonary vascular preparations from rats. 2. SCA40 relaxed ring preparations of main and intralobar pulmonary artery precontracted submaximally with either phenylephrine or U46619 (thromboxane-mimetic). Based on negative log EC50 values, SCA40 was six-to 14-fold more potent than the PDE III inhibitor milrinone or the non-selective PDE inhibitor 3-isobutyl-1-methyl xanthine (IBMX). The potency of SCA40 corresponded to its reported potency as a PDE III inhibitor. 3. In isolated perfused lungs, SCA40 reversed the vasoconstriction induced by alveolar hypoxia. It was 49-fold more potent than IBMX. 4. In main pulmonary artery the vasorelaxation induced by SCA40 was not blocked by the large-conductance calcium-activated potassium channel (BKCa) inhibitors iberiotoxin (50 and 100 nmol/L) or charybdotoxin (100 and 300 nmol/L). This was in contrast to data on guinea-pig trachea, where responses to SCA40 were significantly inhibited by charybdotoxin (100 nmol/L). 5. It is concluded that opening of BKCa channels does not contribute to the pulmonary vasorelaxant effects of SCA40 in main pulmonary artery and it is likely that responses reflect the PDE III inhibitory properties of the drug. 6. It is postulated that SCA40 may be useful as a pulmonary vasodilator in disorders such as pulmonary hypertension.

1-Methyl-3-isobutylxanthine↗

PubMed1986

Local cerebral glucose utilisation following indoleamine- and piperazine-containing 5-hydroxytryptamine agonists.

Substances with varying structural components have been shown to have 5-hydroxytryptamine (5-HT)-like properties in the CNS. In this study, putative 5-HT agonists with indoleamine moeities--lysergic acid diethylamide (LSD) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)--and with piperazine moieties--quipazine (Quip) and 6-chloro-2-(1-piperazinyl)pyrazine (6-CPP) were administered to rats. Local cerebral glucose utilisation was measured using the [14C]2-deoxyglucose autoradiographic technique. It was found that in most cerebral structures, these substances produced dose-dependent reductions in glucose utilisation. However, Quip and 6-CPP increased glucose utilisation in specific areas of the diencephalon (e.g., nucleus reuniens) and produced a biphasic effect in some but not all extrapyramidal structures (e.g., ventromedial caudate nucleus). No such increases in local cerebral glucose utilisation were measured following LSD or 5-MeODMT administration. These results indicate that although similarities exist between the effects of indoleamine- and piperazine-containing 5-HT agonists on local cerebral glucose utilisation there are also significant differences in the overall patterns of response produced.

Animals↗

PubMed1993

Evaluation of the relaxant effects of SCA40, a novel charybdotoxin-sensitive potassium channel opener, in guinea-pig isolated trachealis.

1. Experiments have been performed in order to analyse the mechanism whereby SCA40, a new imidazo[1,2-a]pyrazine derivative relaxes airway smooth muscle. 2. SCA40 (0.01-10 microM) caused a complete and concentration-dependent relaxation of guinea-pig isolated trachea contracted with 20 mM KCl but failed to inhibit completely the spasmogenic effects of 80 mM KCl. 3. Quinine (30 microM) antagonized the relaxant activity of SCA40 in 20 mM KCl-contracted guinea-pig isolated trachea. The ATP-sensitive K(+)-channel blocker, glibenclamide (3 microM), did not antagonize the relaxant activity of SCA40 in either 20 mM KCl or 1 microM carbachol-contracted isolated trachea. 4. SCA40 (0.01-10 microM) and isoprenaline (0.1 nM-10 microM) caused a complete and concentration-dependent relaxation of guinea-pig isolated trachea contracted with carbachol 1 microM. 5. The large-conductance Ca(2+)-activated K(+)-channel blocker, charybdotoxin (60-180 nM), non-competitively antagonized the relaxant activity of isoprenaline on 1 microM carbachol-contracted trachea. The inhibition was characterized by rightward shifts of the isoprenaline concentration-relaxation curves with depression of their maxima. 6. The relaxant activity of SCA40 in 1 microM carbachol-contracted trachea was antagonized by charybdotoxin (60-600 nM) in an apparently competitive manner. The concentration-relaxation curves to SCA40 were shifted to the right with no significant alteration in the maximum response. 7. It is concluded that SCA40 is a novel potassium channel opener which is a potent relaxant of guinea-pig airway smooth muscle in vitro. The relaxant activity of SCA40 does not involve ATP-sensitive K+-channels but rather large-conductance Ca2'-activated K+-channels or other charybdotoxin sensitive K+-channels.

Animals↗

PubMed1978

Isolation and identification of the fluorescent degradation product of some beta-lactam antibiotics.

A fluorescent degradation product of cephalexin, recently employed in the determination of this antibiotic in aqueous solution and human plasma, has been isolated and identified as 2-hydroxy-3-phenyl-6-methylpyrazine. Spectroscopically and chromatographically the product is indistinguishable from that obtained by the same method from a series of other cephalosporins and penicillins bearing an alpha-amino group on the side-chain, and from the pyrazine structure produced by synthesis. Two reported methods for the fluorimetric determination of ampicillin have also been found to yield the same degradation product and not the suggested diketopiperazine structure.

Cephalosporins↗

PubMed1998

Affinity constants and beta-adrenoceptor reserves for isoprenaline on cardiac tissue from normotensive and hypertensive rats.

To determine whether there are differences in cardiac beta-adrenoceptor responsiveness, isoprenaline affinity constants and fractional beta-adrenoceptor occupancy-response relationships for isoprenaline in the early stages of established hypertension, we studied the effects of bromoacetylalprenololmenthane (BAAM) and ([3,5-diamino-6-chloro-N-(1[N-beta-(2-hydroxyl-3-alpha-naphthoxypropy lamino)ethylcarbamoyl]-1-methylethyl)-pyrazine-2-carboxamide (ICI 147 798), slowly reversible beta-adrenoceptor antagonists, on the isoprenaline responses of the left ventricular papillary muscle and the left and right atria of 6-month-old Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The papillary muscles, but not the right and left atria, of the SHR were less responsive to isoprenaline than those of the WKY. The isoprenaline pD2 values (the negative logarithms of the molar concentrations of agonist producing 50% of the maximum response) were 7.72 and 8.00 on the SHR and WKY papillary muscles, respectively. On the WKY papillary muscle the isoprenaline KA values were 2-3 x 10(-6) M, which is as expected for isoprenaline at beta1 or beta2-adrenoceptors. Isoprenaline had 100-fold greater affinity on the WKY and SHR left atria than on the papillary muscles; the isoprenaline KA values were 2-4 x 10(-8) M. On the WKY papillary muscle and left atrium, isoprenaline had to occupy 3-4% of the beta-adrenoceptors to produce a 50% maximum response; on the WKY papillary muscle and left atrium isoprenaline had to occupy 25-35% and 55%, respectively, of the beta-adrenoceptors to produce a 90% maximum response. The SHR papillary muscles and left atrium had smaller beta-adrenoceptor reserves for isoprenaline than did the WKY tissues. We were unable to obtain isoprenaline KA values on the WKY right atrium. The isoprenaline KA value on the SHR right atrium was 1-4 x 10(-8) M. Because the isoprenaline KA values for the left and right atria are markedly different from those previously reported for isoprenaline at beta1 or beta2-adrenoceptors, we suggest that atypical beta-adrenoceptors might be present on the atria of WKY and SHR. We have also demonstrated a lower beta-adrenoceptor reserve on SHR papillary muscle and atria in the early stages of established hypertension.

Adrenergic beta-Agonists↗

PubMed2005

Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites.

Bortezomib [N-(2,3-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid] is a potent first-in-class dipeptidyl boronic acid proteasome inhibitor that was approved in May 2003 in the United States for the treatment of patients with relapsed multiple myeloma where the disease is refractory to conventional lines of therapy. Bortezomib binds the proteasome via the boronic acid moiety, and therefore, the presence of this moiety is necessary to achieve proteasome inhibition. Metabolites in plasma obtained from patients receiving a single intravenous dose of bortezomib were identified and characterized by liquid chromatography/mass spectrometry (LC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Metabolite standards that were synthesized and characterized by LC/MS/MS and high field nuclear magnetic resonance spectroscopy (NMR) were used to confirm metabolite structures. The principal biotransformation pathway observed was oxidative deboronation, most notably to a pair of diastereomeric carbinolamide metabolites. Further metabolism of the leucine and phenylalanine moieties produced tertiary hydroxylated metabolites and a metabolite hydroxylated at the benzylic position, respectively. Conversion of the carbinolamides to the corresponding amide and carboxylic acid was also observed. Human liver microsomes adequately modeled the in vivo metabolism of bortezomib, as the principal circulating metabolites were observed in vitro. Using cDNA-expressed cytochrome P450 isoenzymes, it was determined that several isoforms contributed to the metabolism of bortezomib, including CYP3A4, CYP2C19, CYP1A2, CYP2D6, and CYP2C9. The development of bortezomib has provided an opportunity to describe the metabolism of a novel boronic acid pharmacophore.

Boronic Acids↗

PubMed2007

Disposition of the dipeptidyl peptidase 4 inhibitor sitagliptin in rats and dogs.

The pharmacokinetics, metabolism, and excretion of sitagliptin [MK-0431; (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine], a potent dipeptidyl peptidase 4 inhibitor, were evaluated in male Sprague-Dawley rats and beagle dogs. The plasma clearance and volume of distribution of sitagliptin were higher in rats (40-48 ml/min/kg, 7-9 l/kg) than in dogs ( approximately 9 ml/min/kg, approximately 3 l/kg), and its half-life was shorter in rats, approximately 2 h compared with approximately 4 h in dogs. Sitagliptin was absorbed rapidly after oral administration of a solution of the phosphate salt. The absolute oral bioavailability was high, and the pharmacokinetics were fairly dose-proportional. After administration of [(14)C]sitagliptin, parent drug was the major radioactive component in rat and dog plasma, urine, bile, and feces. Sitagliptin was eliminated primarily by renal excretion of parent drug; biliary excretion was an important pathway in rats, whereas metabolism was minimal in both species in vitro and in vivo. Approximately 10 to 16% of the radiolabeled dose was recovered in the rat and dog excreta as phase I and II metabolites, which were formed by N-sulfation, N-carbamoyl glucuronidation, hydroxylation of the triazolopiperazine ring, and oxidative desaturation of the piperazine ring followed by cyclization via the primary amine. The renal clearance of unbound drug in rats, 32 to 39 ml/min/kg, far exceeded the glomerular filtration rate, indicative of active renal elimination of parent drug.

Adenosine Deaminase↗

PubMed2007

Characterization of two cyclic metabolites of sitagliptin.

Two novel metabolites of the dipeptidyl peptidase inhibitor sitagliptin (MK-0431, (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)-butan-2-amine), were identified after purification from dog urine. The metabolites (referred to as M2 and M5) were characterized by hydrogen/deuterium exchange tandem mass spectrometry and NMR spectroscopy nuclear Overhauser effect experiments as the cis and trans stereoisomers formed by cyclization of the primary amino group with the alpha carbon of the piperazine ring, following oxidative desaturation.

Animals↗

PubMed2003

Hyperlocomotive and discriminative stimulus effects of cocaine are under the control of serotonin(2C) (5-HT(2C)) receptors in rat prefrontal cortex.

The serotonin2C (5-hydroxytryptamine2C; 5-HT2C) receptor (5-HT2CR) is found in abundance in dopamine (DA) mesocorticolimbic pathways and is one of the important target proteins that modulates the behavioral effects of cocaine. In the present study, the hypothesis was tested that the 5-HT2CR in the prefrontal cortex (PFC) may control either spontaneous or cocaine-evoked locomotor activity as well as the discriminative stimulus properties of cocaine. In male Sprague-Dawley rats implanted with bilateral cannulae aimed at the PFC, local microinjections of the preferential 5-HT2CR agonist 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK 212) (0.05-0.5 microg/side) did not alter spontaneous activity, but dose-dependently decreased horizontal hyperactivity evoked by cocaine (10 mg/kg i.p.). Given alone, the selective 5-HT2CR antagonist 8-[5-(2,4-dimethoxy-5-(4-trifluorophenylsulfonamido)phenyl-5-oxopentyl]-1,3,8-triazo-spiro[4.5]decane-2,4-dione hydrochloride (RS 102221) (5 microg/side) increased basal locomotor activity of rats expressed in the vertical plane. Microinjections of RS 102221 (5 microg/side, but not 0.15-1.5 microg/side) significantly enhanced the horizontal activity induced by cocaine (10 mg/kg). In rats trained to discriminate cocaine (10 mg/kg i.p.) from saline (i.p.) in a two-lever, water-reinforced fixed ratio 20 task, intra-PFC microinjections of MK 212 (0.05 and 0.5 microg/side) did not substitute for cocaine, but attenuated the stimulus effects of cocaine. However, intra-PFC microinjections of RS 102221 (1.5 and 5 microg/side) evoked 13 and 40% cocaine-lever responding when tested alone and enhanced the recognition of cocaine. These data indicate that the PFC is a brain site at which the 5-HT2CR exerts an inhibitory control over the hyperactive and discriminative stimulus effects of cocaine known to be dependent upon activation of the DA mesoaccumbens circuit.

Animals↗

PubMed2004

Contribution of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes to the hyperlocomotor effects of cocaine: acute and chronic pharmacological analyses.

The role of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes (5-HT2AR, 5-HT2BR, and 5-HT2CR) in acute cocaine-evoked hyperactivity was compared with their contribution to the development and expression of locomotor sensitization upon repeated, intermittent treatment with cocaine (10 mg/kg/day for 5 days) in male Wistar rats. Cocaine-evoked hyperactivity was significantly enhanced by pretreatment with the preferential 5-HT2AR agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT2CR antagonist SDZ SER-082 [(+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo(1,7-BC)(2,6) naphthyridine fumarate]. The 5-HT2AR antagonist SR 46349B [1(Z)-[2-(dimethylamino)ethoxyimino]-1(2-fluorophenyl)-3-(4-hydroxyphenyl)-2(E)-propene] and the preferential 5-HT2CR agonist MK 212 [6-chloro-2-(1-piperazinyl)pyrazine HCl] (2 mg/kg) significantly attenuated acute cocaine-evoked hyperactivity; however, a lower dose of MK 212 (0.3 mg/kg) enhanced cocaine-evoked hyperactivity. The 5-HT2BR agonist BW 723C86 (1-[5-(2-thienylmethoxy)-1H-3-indolyl]propan-2-amine HCl) and the 5-HT2BR antagonist SB 204741 [N-(1-methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl) urea] had no effect on cocaine-evoked hyperactivity. Repeated treatment with cocaine alone resulted in a 2-fold increase in hyperactivity upon challenge with cocaine 5 days after termination of the cocaine regimen (sensitization). The 5-HT2AR antagonist SR 46349B also blocked cocaine-evoked hyperactivity following repeated cocaine treatment, whereas the other 5-HT2R ligands were ineffective. When any of the 5-HT2R ligands was coadministered with cocaine during the treatment regimen (10 mg/kg/day for 5 days), the development of sensitization was unchanged as measured by the level of cocaine-evoked hyperactivity upon challenge 5 days after termination of the treatment. The present study implies that 5-HT2AR and 5-HT2CR exert oppositional influence upon hyperactivity evoked by acute administration of cocaine; this balance is altered following repeated cocaine administration.

Amphetamines↗

PubMed2005

Mechanism of action of T-705 against influenza virus.

T-705, a substituted pyrazine compound, has been found to exhibit potent anti-influenza virus activity in vitro and in vivo. In a time-of-addition study, it was indicated that T-705 targeted an early to middle stage of the viral replication cycle but had no effect on the adsorption or release stage. The anti-influenza virus activity of T-705 was attenuated by addition of purines and purine nucleosides, including adenosine, guanosine, inosine, and hypoxanthine, whereas pyrimidines did not affect its activity. T-705-4-ribofuranosyl-5'-triphosphate (T-705RTP) and T-705-4-ribofuranosyl-5'-monophosphate (T-705RMP) were detected in MDCK cells treated with T-705. T-705RTP inhibited influenza virus RNA polymerase activity in a dose-dependent and a GTP-competitive manner. Unlike ribavirin, T-705 did not have an influence on cellular DNA or RNA synthesis. Inhibition of cellular IMP dehydrogenase by T-705RMP was about 150-fold weaker than that by ribavirin monophosphate, indicating the specificity of the anti-influenza virus activity and lower level of cytotoxicity of T-705. These results suggest that T-705RTP, which is generated in infected cells, may function as a specific inhibitor of influenza virus RNA polymerase and contributes to the selective anti-influenza virus activity of T-705.

Amides↗

PubMed2006

Degradation of 2,3-diethyl-5-methylpyrazine by a newly discovered bacterium, Mycobacterium sp. strain DM-11.

A bacterium was isolated from the waste gas treatment plant at a fishmeal processing company on the basis of its capacity to use 2,3-diethyl-5-methylpyrazine (DM) as a sole carbon and energy source. The strain, designated strain DM-11, grew optimally at 25 degrees C and had a doubling time of 29.2 h. The strain did not grow on complex media like tryptic soy broth, Luria-Bertani broth, or nutrient broth or on simple carbon sources like glucose, acetate, oxoglutarate, succinate, or citrate. Only on Löwenstein-Jensen medium was growth observed. The 16S rRNA gene sequence of strain DM-11 showed the highest similarity (96.2%) to Mycobacterium poriferae strain ATCC 35087T. Therefore, strain DM-11 merits recognition as a novel species within the genus Mycobacterium. DM also served as a sole nitrogen source for the growth of strain DM-11. The degradation of DM by strain DM-11 requires molecular oxygen. The first intermediate was identified as 5,6-diethyl-2-hydroxy-3-methylpyrazine (DHM). Its disappearance was accompanied by the release of ammonium into the culture medium. No other metabolite was detected. We conclude that ring fission occurred directly after the formation of DHM and ammonium was eliminated after ring cleavage. Molecular oxygen was essential for the degradation of DHM. The expression of enzymes involved in the degradation of DM and DHM was regulated. Only cells induced by DM or DHM converted these compounds. Strain DM-11 also grew on 2-ethyl-5(6)-methylpyrazine (EMP) and 2,3,5-trimethylpyrazine (TMP) as a sole carbon, nitrogen, and energy source. In addition, the strain converted many pyrazines found in the waste gases of food industries cometabolically.

Biodegradation, Environmental↗

PubMed1973

Volatile compounds produced in sterile fish muscle (Sebastes melanops) by Pseudomonas perolens.

Volatile compounds produced by Pseudomonas perolens ATCC 10757 in sterile fish muscle (Sebastes melanops) were identified by combined gas-liquid chromatography and mass spectrometry. Compounds positively identified included methyl mercaptan, dimethyl disulfide, dimethyl trisulfide, 3-methyl-1-butanol, butanone, and 2-methoxy-3-isopropylpyrazine. Compounds tentatively identified included 1-penten-3-ol and 2-methoxy-3-sec-butylpyrazine. The substituted pyrazine derivative 2-methoxy-3-isopropylpyrazine was primarily responsible for the musty, potato-like odor produced by P. perolens.

Alcohols↗

PubMed1975

Determination of the active portion of the folic acid molecule in cellular slime mold chemotaxis.

From earlier work it is known that folic acid attracts the amoebae of various species of cellular slime molds (11). Here we have tested a wide variety of pteridines, pyrimidines, and pyrazines to determine what part of the folic acid molecule is chemotactically active. It was shown that the activity lies in the pteridine ring itself. Furthermore, the cell-free supernatants of slime mold amoebae contain an enzyme that renders pterin and folic acid chemotactically inactive, which apparently increases the chemotactic sensitivity of the amoebae to those compounds. Despite the fact that slime mold amoebae secrete small amounts of folic acid-related compounds, there is no evidence that folates are acrasins; rather it is postulated that attraction to folates may be a food-seeking device for the amoebae which prey on folate-secreting bacteria in the soil.

Agar↗

PubMed1993

ICI 206,970: a novel calcium channel blocker with eukalemic diuretic activity.

ICI 206,970 is a novel eukalemic diuretic from the aminomethylphenol pyrazine series which exhibited a calcium antagonist profile. The isolated rat aorta evaluation and dihydropyridine ligand [3H]-PN 200-110 binding studies demonstrated that ICI 206,970, like verapamil and nifedipine, inhibits vascular smooth muscle tone by inhibiting voltage-sensitive calcium channels. ICI 206,970 produced dose-related hypotensive, negative chronotropic, dromotropic, and coronary vasodilator responses after i.v. injection in anesthetized dogs. ICI 206,970, similar to calcium channel blockers and dissimilar to diuretics, produced an acute antihypertensive effect in spontaneously hypertensive rats (SHR), and significant protection against the development of myocardial hypertrophy in SHR after chronic oral treatment for 28 consecutive days. It is concluded that ICI 206,970 is a calcium channel blocker in addition to its novel eukalemic diuretic property.

Animals↗

PubMed1994

Diuretic and antihypertensive activity of ZENECA ZM224,832: a novel eukalemic diuretic with calcium channel blocking activity.

ZENECA ZM224,832 is a novel eukalemic diuretic from the aminomethylphenol pyrazine series which demonstrated a profile of calcium channel blockers. It produced diuretic and saluretic effects in animals but had only minimal alterations in kaliuresis after oral administration. In contrast to standard diuretics, the plasma K+ concentration was not altered in conscious dogs treated for 14 days with ZENECA ZM224,832 and the concurrent plasma renin activity was also minimally elevated. The isolated rat aorta evaluation indicated that ZENECA ZM224,832, like tiapamil and nifedipine, inhibited vascular smooth muscle tone by inhibiting voltage-dependent calcium channels. ZENECA ZM224,832 produced a dose-dependent decrease of blood pressure in spontaneously hypertensive rats (SHR) in which the antihypertensive activity was not noted with HCTZ. In addition, ZENECA ZM224,832, similar to diltiazem, produced an acute blood pressure lowering effect in nephrectomized SHR which was independent of its diuretic activity. It is concluded that ZENECA ZM224,832 is a potent eukalemic diuretic with calcium channel blocking properties.

Animals↗

PubMed1991

Ability of polymorphonuclear leukocytes to generate active oxygen species in children with bronchial asthma. Use of chemiluminescence probes with a Cypridina luciferin analog and luminol.

Airway inflammation with polymorphonuclear leukocytes (PMN) may play an important role in bronchial hyperresponsiveness (BHR). PMN generate superoxide anion (O2-) and other oxygen radicals that can damage lung tissue. We investigated the ability of peripheral PMN of children with bronchial asthma and control subjects to generate O2- and other active oxygen species using a 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one, a highly sensitive and specific chemiluminescence (CL) probe for O2-, and luminol-dependent CL. The ability of PMN of subjects with asthma to generate O2- and other active oxygen species was significantly greater than that of PMN of control subjects when stimulated with opsonized zymosan (OZ), phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine. Furthermore, in the same asthmatic children, the generation of O2- and other active oxygen species was significantly higher with attacks than without attacks when PMN were stimulated with OZ. We also demonstrated that O2- generation correlated with the degree of BHR to inhaled histamine. These results suggest that PMN of asthmatic children, especially those with attacks, generate more active oxygen species than that of control subjects and that airway inflammation caused by O2- may be closely related to BHR in subjects with bronchial asthma.

Adolescent↗

PubMed1979

Central serotonergic agents raise the repetitive extrasystole threshold of the vulnerable period of the canine ventricular myocardium.

Systemic administration of three central serotonergic agents, melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), produced significant increases in the threshold of the vulnerable period for repetitive electrical activity in the canine cardiac ventricle. MK-212 was effective despite bilateral vagotomy. The specific serotonin antagonist, metergoline, blocked the effect of MK-212 on the threshold. An increase in central serotonergic activity may inhibit the flow of arrhythmogenic sympathetic nerve traffic from the brain to the heart.

Animals↗