SEARCH · PubMed Health

Results for “IPRONIAZID”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources

PubMed1967

The responses of thalamic neurons to iontophoretically applied monoamines.

1. The effects of noradrenaline (NA), adrenaline, dopamine (DA) 5-hydroxytryptamine (5-HT) and a number of related drugs were tested on the extracellularly recorded responses of neurones in the feline thalamus. Substances were applied iontophoretically and tested on synaptically, antidromically and chemically evoked neuronal activity.2. NA, adrenaline, isoprenaline and 5-HT had a variety of effects, depressing some cells, exciting others and not affecting the responses of a third group. DA depressed most of the cells tested; excitation was not observed with this compound.3. The magnitude of depressant actions and their duration varied considerably. The more sensitive cells responded to extremely small amounts of catecholamine or 5-HT and recovery often took several minutes. Recovery after DA was always rapid. Neurones in the dorsal thalamus were generally more susceptible to depression than those in the ventro-basal complex.4. Excitatory responses were most marked in the ventro-basal complex of the thalamus. Desensitization occurred if NA or adrenaline was applied repeatedly and this tachyphylaxis lasted for several minutes. After desensitization to the excitatory effects, some of these cells were depressed by catecholamines. These findings suggest the presence of at least two types of membrane receptor.5. beta-adrenergic antagonists (alderlin, D-INPEA and MJ 1999) and alpha-antagonists (phentolamine, dibenzyline and chlorpromazine) had pronounced depressant actions on some thalamic neurones. With the exceptions of D-INPEA and MJ 1999 they also excited cells that were excited by the catecholamines. Alderlin and phentolamine had both excitatory and inhibitory effects on some cells.6. The monoamine oxidase inhibitor, iproniazid, depressed neurones which were sensitive to NA depression. It did not appear to potentiate the effects of NA on most of the cells tested.7. Reticular formation stimulation depressed some neurones in the thalamus and excited others. The depressant effects of NA and reticular formation stimulation were reduced or abolished by an intravenous injection of picrotoxin (1 mg/kg).8. It is suggested that NA and 5-HT may be inhibitory transmitters in the thalamus, released at the terminals of ascending pathways from the brain stem that have been defined by fluorescence microscopy. The excitatory actions of these compounds may also be related to a synaptic role.

Acetylcholine↗

PubMed1970

Serotonin-containing neurons in brain: depression of firing by monoamine oxidase inhibitors.

Monoamine oxidase inhibitors were administered to rats while the activities of single, serotonin-containing neurons of the midbrain raphe nuclei were being monitored with microelectrodes. All the inhibitors tested (pargyline, tranylcypromine, phenelzine, iproniazid) caused depression of raphe unit firing rate. The ability of monoamine oxidase inhibitors to depress raphe units was impaired by prior treatment with p-chlorophenylalanine, an inhibitor of serotonin synthesis.

Animals↗

PubMed1986

Serotonin uptake by bovine pulmonary artery endothelial cells in culture. II. Stimulation by hypoxia.

Exposure of bovine pulmonary artery endothelial cells to 3% O2 resulted in approximately twofold stimulation of serotonin (5-HT) uptake after 24-48 h when compared with cells exposed to 20% O2. The enhanced uptake was reversed after 48 h when cells were again placed in 20% O2. The stimulation was not observed after 0.5 or 2 h of exposure to hypoxia. The stimulation was present when iproniazid blocked conversion of 5-HT to 5-hydroxyindole-3-acetic acid, indicating that enhanced uptake did not occur through augmentation of monoamine oxidase activity. Stimulation of uptake by hypoxia occurred at low concentrations of 5-HT (up to 10(-6) M) but not at high 5-HT concentrations (greater than 10(-5) M) and was blocked by imipramine or absence of sodium from the medium, indicating that high-affinity transport and not diffusion of 5-HT was stimulated. Furthermore, exposure of cells to hypoxia did not produce morphological evidence of injury or change in protein content or trypan blue exclusion. The cell number of 3% O2-exposed cells was slightly reduced when compared with controls after 48 h. There was no change in cellular ATP or increase in lactate dehydrogenase in medium of cells exposed to 3% O2. Thus exposure of endothelial cells in culture to hypoxia stimulates the membrane activity of 5-HT accumulation with no evidence of injury to the cell.

Adenosine Triphosphate↗

PubMed1975

Depression of pulmonary 5-hydroxytryptamine uptake by metabolic inhibitors.

Energy requirements for uptake of 14-C labeled 5-hydroxytryptamine ([14-C]5-HT) were studied in isolated guinea pig lungs, ventilated with 95% O2-5% CO2 and perfused in a recirculating system with Krebs-Ringer-bicarbonate solution containing 4% bovine serum albumin and 5 mM glucose. After 14 min preincubation with various inhibitors, lungs were perfused for 30 min with 0.25 times 10- minus 6 M [14-C]5-HT. Aliquots of perfusate were analyzed for [14-C]5-HT and metabolic products. Control lungs had a fractional serotonin clearance of 0.57 plus or minus 0.04. The rate of removal of [14-C]5-HT was inhibited 96% by imipramine, 88% by chlorpromazine, and 65% by ouabain, but was unaffected by iproniazid. Anoxia and cyanide each inhibited uptake by 68%. Omitting glucose from the perfusate reduced uptake by 30%. 2-Deoxyglucose and iodoacetate decreased the rate of [14-C]5-HT removal by 44 and 70%, respectively. Uptake was not affected by lung weight gain nor by changes in lung mechanical properties produced by [14-C]5-HT. [14-C]5-HT uptake by guinea pig lung requires a metabolic source of energy providing additional evidence for transport by an active process.

Animals↗

PubMed1981

Depression of serotonin uptake by cultured endothelial cells exposed to high O2 tension.

Serotonin (5-hydroxytryptamine, 5-HT), a vasoactive amine, is removed from the pulmonary circulation by active transcellular transport into endothelial cells, followed by intracellular metabolism. Pulmonary uptake of 5-HT is depressed by high partial pressures of O2 (Po2). To characterized the cellular basis and mechanism for hyperoxic depression of lung 5-HT uptake, we evaluated the effect of high Po2 on 5-HT uptake by calf aortic endothelial cells in primary confluent monolayer. Cells were exposed to either 95% O2, or 14% O2 (controls) in 5% Co2 at 1 ATA for 20 or 42 h. Following exposure 5-[14C]HT (1 X 10-7 M) was added to the culture medium, and 5-HT uptake in pmol/10(6) cells was measured. Exposure to 95% O2 for 20 h or 42 H resulted in significant depression of 5-HT uptake by cultured endothelial cells, and uptakes remained significantly depressed 48 h after exposure to 95% O2 had ended. Inhibition of intracellular metabolism of 5-HT by iproniazid did not affect 5-HT uptake by control or O2-exposed endothelial cells. These results indicate that 1) high Po2 levels depress 5-HT uptake in endothelial cells by direct inhibition of the transcellular transport of 5-HT and 2) hyperoxic depression of 5-HT uptake in cultured endothelial cells is not readily reversible.

Animals↗

PubMed1982

Effects of drug pretreatment on antipyrine elimination in the rabbit.

Iproniazid (25-100 mg/kg) produced a marked, dose-related reduction in antipyrine elimination in the rabbit, whereas reductions produced by nitrazepam (32 mg/kg) or SKF 525A (25 and 40 mg/kg) were small. Phenobarbitone, 10 mg/kg chronically, increased antipyrine elimination. The small inhibitory effect of SKF 525A on antipyrine metabolism in the rabbit was unexpected compared to the marked effect in the rat.

Animals↗

PubMed1977

Uptake and metabolism of noradrenaline by the mesenteric arteries of the dog.

Uptake and metabolism of tritiated noradrenaline by the mesenteric arteries of the dog and concomitant behaviour changes in endogenous noradrenaline are described. Posterior mesenteric artery strips were incubated for 30 min in Krebs solution containing (-)-7-3H-noradrenaline (1,084 muM); suitable pretreatments and/or preincubations were performed to study the influence of some drugs on these parameters. The atrial strips showed a high capacity to retain, accumulate and metabolize exogenous noradrenaline. At the concentration of noradrenaline studied, neuronal uptake and deamination represented the main inactivation mechanism, however, when neuronal uptake was blocked, extraneuronal deamination and o-methylation played a more important role, o-Methylation represented a vicarious enzymatic route when monoamine oxidase activity was inhibited. Iproniazid pretreatment increased markedly the endogenous noradrenaline content of the mesenteric arteries. During incubation with tritiated noradrenaline both an outflow of endogenous noradrenaline and an inflow of tritiated noradrenaline were observed.

Animals↗

PubMed1981

Uptake and metabolism of noradrenaline by blood vessels of perinephritic hypertensive dogs.

Tissue noradrenaline content as well as uptake and metabolism of tritiated exogenous noradrenaline were studied comparatively, in vitro in mesenteric arteries, and in saphenous veins of normotensive and perinephritic hypertensive dogs. The influence of cocaine, iproniazid and 3'-4'-dihydroxy-2-methyl-propiophenone (U-0521) on these variables was also investigated. The concentration of (-)-7-3H-noradrenaline used was 1.08 microM. No changes were observed in noradrenaline content, uptake and metabolism in saphenous vein strips obtained from normotensive or hypertensive animals. However, in mesenteric artery strips obtained from hypertensive dogs, a marked reduction in endogenous noradrenaline content was observed as well as a reduction in noradrenaline accumulation (20 weeks after surgery). The deamination pattern was also modified in these strips: the formation of DOPEG was markedly diminished and the formation of DOMA was increased. These results agree well with the degeneration of the sympathetic innervation of the mesenteric arteries of hypertensive dogs described by Azevedo et al. (1981).

Animals↗

PubMed1975

Serotonin transport by cultured bovine aortic endothelium.

Endothelial cells isolated from bovine aortas without prior treatment with enzymes were cultured in RPMI 1640 medium containing 17% fetal calf serum and antibiotics. The endothelial cells at confluency (7 days) were similar to endothelium in situ or to freshly isolated endothelial cells from blood vessels as seen by light, scanning, and electron microscopy. Cultured and freshly isolated indothelial cells exposed to labeled serotonin, even in the presence of iproniazid (5 x 10-4M), took up approximately 125 and 250 pmoles 14C-serotonin/mg protein, respectively, in 3 hours. Imipramine (10-4M) reduced uptake for both cell groups. Cold (4 degrees C) and metabolic inhibitors sharply reduced serotonin uptake by both freshly isolated and cultured endothelial cells. Ouabain (10-5M) almost completely blocked serotonin transport. Six analogues of serotonin at concentrations ten times above experimental serotonin concentrations did not affect serotonin transport in the cultured endothelial cells but did reduce it in the freshly isolated endothelial cells by 50%. The data on transport suggest that serotonin uptake is not unique to pulmonary endothelium, as has been suggested previously. In addition, using cultured indothelial cells to study serotonin transport is compatible with using other serotonin model systems such as platelets, lung, or brain. Lastly, serotonin uptake by endothelial cells may involve an active transport mechanism similar to that described for the pulmonary circulation, platelets, and insect salivary glands.

Animals↗

PubMed1990

Metabolism of diltiazem. III. Oxidative deamination of diltiazem in rat liver microsomes.

The main metabolites of diltiazem in rats are acidic metabolites having a carboxyl group which may be formed by oxidative deamination of the dimethylaminoethyl group of diltiazem. In order to identify the enzymes responsible for the deamination and formation of acidic and neutral metabolites [14C]diltiazem was incubated with microsomal and mitochondrial preparations from the liver of SD male rats. Both acidic and neutral metabolites were formed only in the presence of an nicotinamide adenine dinucleotide phosphate generating system. Their formation was remarkable, especially in the microsomes, and inhibited by SKF 252-A, but not by pargyline and iproniazid. The production of neutral metabolites surpassed that of acidic ones. Structural analysis by gas chromatography-mass spectrometry showed that the neutral metabolites are aldehydes which have not been detected in vivo. The results suggest that the dimethylaminoethyl group of diltiazem is oxidized to an aldehyde group by microsomal cytochrome P-450 in the liver. Subsequently, the aldehyde group would be dehydrogenated to the carboxyl group.

Animals↗

PubMed1976

The role of biotransformation in chemical-induced liver injury.

The role of drug metabolism in chemical-induced liver injury is reviewed. Parameters for studying the formation of chemically reactive metabolites are discussed and the factors that alter the formation and covalent binding of reactive metabolites are selectively emphasized. Some of the experimental work that led to these concepts is discussed, especially the chemical toxicology of the hepatic injury produced by acetaminophen, bromobenzene, furosemide, isoniazid and iproniazid.

Acetaminophen↗

PubMed1979

Experimental aggression and bruxism in rats.

Aggression has been suggested as one of the etiologic factors in bruxism. Experimental bruxism, audible, nonfunctional grinding or clenching of the teeth, was provoked in aggressive animals by drugs affecting central dopaminergic systems. Electric foot-stimulation was used to induce aggression, evident as the threatening or fighting position, in paired male Wistar rats. After initial stimulation, shocks were given only to maintain the characteristic fighting pose. Apomorphine facilitated induction of aggressive behaviour by electric shocks, and the rats receiving both treatments showed bruxism more frequently than controls subjected to shocks alone: up to 95 bruxism periods registered by a tape recorder during 30 min, as opposed to a few sporadic periods in the controls. Without shocks, apomorphine-treated rats displayed stereotypy with locomotion and biting of various objects. Aggression and bruxism were not equally successfully induced after L-dopa given with a peripheral inhibitor of aromatic amino acid decarboxylase (benserazide) or when L-dopa treatment was modified with the inhibitor of dopamine-beta-hydroxylase (diethyldithiocarbamate) or monoamine oxidase inhibitor (iproniazid). However, all the present drug combinations known to enhance central dopaminergic function seemed to increase irritability and disposition to experimental oral dyskinesias. This was observed especially when a sensory stimulus was applied at the same time or the drug had an amine-releasing effect (pheniprazine).

Aggression↗

PubMed1981

Response of the isolated rabbit ciliary epithelium to adrenergic drugs following superior cervical ganglionectomy.

The fluid permeability of the isolated ciliary epithelium of the rabbit eye to adrenergic agonist's has been measured in paired normal and ganglionectomized tissues. The agonists norepinephrine (NE), epinephrine (E), phenylephrine (P) and isoproterenol (ISO) were used at concentrations from 10(-12) to 10(6)M in the presence and absence of cocaine 2.6 or 26x10(-6)M (C, to prevent uptake of agonist in the synapse); iproniazid (I) 3.6 x 10(-5)M, or clorgyline (CL) 5x10(-5)M (to inhibit 10(-5)M, or clorgyline (CL) 5x10(-5)M (to inhibit monoamine oxidase); dibenamine, (D) 1x10(-5) (to block extraneuronal uptake) and/or 1x10(-8)M phenoxybenzamine (PH) (an alpha-adrenergic antagonist). No supersensitivity to adrenergic agonists was found in ganglionectomized tissues. Normal tissues showed an increased fluid permeability after agonist alone with the other of efficacy at 10(-8)M being ISO greater than NE greater than E greater than P, while in ganglionectomized tissues the order at 10(-8)M was E = NE greater than ISO = P. Normal tissues showed a sensitivity to agonists at 10(-8)M in order E greater than NE greater than P greater than ISO after treatment with C, I and D, while ganglionectomized tissues revealed a sensitivity to NE greater than P greater than ISO greater than E, even though the quantitative response after C, I and D was reduced. It appears, therefore, that both alpha- and beta-receptors exist in the ciliary epithelium, and although ganglionectomy alters the tissues responsiveness to different adrenergic agonists it is not the site of the supersensitivity seen in the whole eye.

Animals↗

PubMed1976

[Endogenous catecholamines and excitability of the superior cervical ganglion of the rat (author's transl)].

1. The excitability of the superior cervical ganglion of the rat, as measured by homosynaptic facilitation, was enhanced after a three-day administration of guanethidine (fig. 1) or reserpine (fig. 2). 2. The excitability of the superior cervical ganglion of the rat was not diminished after a three-day treatment with L-Dopa, Benseraside (Ro 4-4602/1) and Iproniazid, at a dosage below the toxic level (table I). 3. The enhancement of ganglionic excitability is assigned to the action of the drugs upon the catecholamines of the chromaffin cells (and their processes) present in the superior cervical ganglion. 4. Except for alpha-methyl-meta-tyrosine, the drugs which were used did not cause any ultrastructural changes on the granules and vesicles of the chromaffin cells (fig. 4). 5. Alpha-methyl-meta-tyrosine did not enhance the ganglionic excitability, but damaged the Golgi complex, the mitochondria and the granules of the chromaffin cells, especially in the para-hilus area. The more peripheral chromaffin cells showed much less ultrastructural damage.

Animals↗

PubMed1976

Role of neuronal and extraneuronal factors in temperature mediated responsiveness of adrenoceptors.

Changes in bath temperature caused changes in the adrenergic responsiveness of rabbit iris dilator muscle as indicated by shifts in dose-response curves along the log axis and changes in maximum responses. Responses of control tissues to an alpha agonist (norepinephrine) were increased at lower temperatures and responses to a beta agonist (isoprenaline) were increased at higher temperatures. Responses of control tissues were compared with responses of tissues pretreated with cocaine or with responses of adrenergically denervated tissues (chemical and surgical). Changes in ED50 values with temperature change are similar in control, cocaine pretreated or denervated muscles. In contrast, changes in maximum response with temperature change are reversed by cocaine pretreatment or denervation. Pretreatment of tissues with an inhibitor of catechol-o-methyl transferase (tropolone) or an inhibitor of monoamine oxidase (iproniazid) did not affect the temperature sensitivity of adrenoceptors. Also, responses to terbutaline, a beta agonist not susceptible to catechol-o-methyl transferase, changed with temperature. These data indicate that for rabbit iris dilator muscle both a neuronal and an extraneuronal component are involved in adrenoceptor response changes induced by temperature change and that changes in rates of activity of metabolizing enzymes are not involved.

Animals↗

PubMed1975

Serotonergic and cholinergic mechanisms during disruption of approach and avoidance behavior.

Injections of D,L-5-hydroxytryptophan (D,L-5-HTP) into pigeons and rats working on approach schedules produce a period of behavioral depression that is temporally correlated to increased levels of total serotonin (5-?HT) in the telencephalon and diencephalon. Administration of alpha-methyl-meta-tyrosine (alpha-MMT) also results in depressed responding; however, the temporal correlation is with decreased levels of total 5-HT in brain. Our hypothesis to explain these two apparent opposite biochemical states which result in similar behavioral disruptions is that in both cases more 5-HT is released within certain key serotonergic synapses mediating this behavior. Evidence from subcellular studies supports this concept. tnot only are the levels of 5-HT significantly higher in preparations of nerve endings isolated from the telencephalon and diencephalon of pigeons given injections of D,L-5-HTP, but in vitro studies also show that low concentrations of L-5-HTP significantly increased the release of radioactive 5-HT from serotonergic nerve endings. On the other hand, L-5-HTP in much higher concentrations had no effect on the release of labeled dopamine or norephinephrine. A major metabolite of alpha-MMT, alpha-methyl meta tyramine, also caused a significant increase in the release of labeled 5-?HT from similar preparations of nerve endings. Whereas serotonin appears to be involved in the disruption of approach behavior, another series of studies have indicated that acetylcholine may play a role in excitation during avoidance behavior. Behavioral excitation observed following administration of tetrabenazine 18 hr after iproniazid pretreatment to rats working on shock-avoidance schedules was temporally correlated with lowered levels of acetylcholine in the telencephalon. Pretreatment with 0.8 mg/kg of atropine blocked excitation whereas one-eight of this dose increased the duration. Excitation in these rats was shortened by 50% following bilateral septal lesions, which lowered brain acetylcholine levels. Mechanisms to explain these neurochemical correlates of behavior are discussed.

5-Hydroxytryptophan↗

PubMed1975

Procaine HCl (Gerovital H3): a weak, reversible, fully competitive inhibitor of monoamine oxidase.

A specially stabilized form of procaine hydrochloride (Gerovital H3) has been shown to be a more potent inhibitor of monoamine oxidase than procaine HCl itself and a weaker inhibitor of this enzyme than iproniazid. This preparation was studied to determine its mode of interaction with monoamine oxidase using purified rat brain mitochondrial monoamine oxidase as the enzyme source. Reaction velocities were determined spectrophotometrically by quantitating the rate of appearance of 4-hydroxyquinoline from kynuramine. Dilutional studies comparing the mechanism of inhibition of monoamine oxidase produced by Gerovital H3 and by ipronizid demonstrated that Gerovital H3 was a reversible inhibitor of monoamine oxidase. Analysis of studies using Lineweaver-Burk and Dixon plots revealed that Gerovital H3 was a fully competitive inhibitor of monoamine oxidase. That Gerovital H3 is a weak, reversible, competitive inhibitor of monoamine oxidase may explain the absence of adverse reactions associated with the clinical use of Gerovital H3 as compared to the severe adverse reactions that have been associated with the use of irreversible monoamine oxidase inhibitors.

Animals↗

PubMed1975

Pharmacological action of FD-008, a new dopamine-beta-hydroxylase inhibitor. III. Effects on endogenous biogenic amine levels in rats.

Effect of a new dopamine beta-hydroxylase inhibitor, 5-(4'-chlorobutyl)-picolinic acid (FD-008) on endogenous amine levels in various tissue of normotensive and spontaneously hypertensive rats were determined in comparison with its mother compound, fusaric acid, and disulfiram. FD-008 decreased norepinephrine (NE) levels in the brain and heart with a slight increase of dopamine (DA) level in the brain. NE lowering activity of FD-008 was stronger than that of fusaric acid. Disulfiram was less active and the activity was one-tenth of FD-008. FD-008 lowered NE level even when DA was increased by pretreatment with L-DOPA or iproniazid but did not cause a further significant reduction of NE when catecholamines were practically depleted by pretreatment with reserpine.

Adrenal Glands↗