Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IPRONIAZID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 559 records · Page 31Linked to original sources
PubMed1980

Monoamine oxidase inhibitors and histamine metabolism.

In rat, histamine metabolism is altered by some nonspecific inhibitors of monoamine oxidase (MAO) such as iproniazid, and, to a lesser extent, tranylcypromine. Type A MAO inhibitors, such as clorgyline and MD780515, do not seem to interfere with the metabolism of histamine. Deprenyl, a type B MAO inhibitor, shows some inhibition which is, however, much lower than that observed with iproniazid. The strong effect of iproniazid is probably due to its DAO inhibiting properties.

Animals↗
PubMed1976

Neurochemical correlates of behavior: levels of amino acids in four areas of the brain of the rat during drug-induced behavioral excitation.

The levels of GABA, aspartate, glutamate, glycine and alanine were determined in 4 specific brain areas (telencephalon, diencephalon-mesencephalon cerebellum and pons-medulla oblongata) of rats killed during a period of drug-induced behavioral excitation. Behavioral excitation was obtained in adult, male Wistar rats working on a Sidman shock-avoidance schedule following administration of 2 mg/kg tetrabenazine (TBZ) 18 hr after iproniazid (50 mg/kg) pretreatment. When compared to trained animals (working on the avoidance schedule but receiving no drugs), the excited rats had increased levels of GABA in the telencephalon and diencephalon-mesencephalon, decreased levels of aspartate in all 4 brain areas, and a lower content of glycine in the pons-medulla region. The changes in the levels of aspartate in all areas of the brain, GABA in the diencephalon-mesencephalon, and glycine in the pons-medulla were significantly correlated (p less than 0.01) with the degree of excitation. It was observed that avoidance training alone produced increases in the levels of four amino acids: aspartate in telencephalon and cerebellum, GABA in cerebellum, and glycine and glutamate in the pons-medulla. The injection of iproniazid alone or iproniazid followed by TBZ into naive animals had little effect on the levels of the five amino acids. The data are discussed in terms of aspartate and GABA interacting as neurotransmitters with cholinergic and catecholaminergic and/or serotonergic neurons to produced the behavioral excitation.

Amino Acids↗
PubMed1991

Spectrophotometric determination of some MAO inhibitors using 7,7,8,8-tetracyanoquinodimethane and iodine monochloride.

Two simple and sensitive spectrophotometric methods are described for the assay of three MAO inhibitors: isocarboxazid, tranylcypromine sulphate and iproniazid phosphate. The first method is based on the formation of a highly coloured stable radical anion between the drug as an n-donor and 7,7,8,8-tetracyanoquinodimethane (TCNQ) as a pi-electron acceptor. Beer's law is obeyed in the concentration range 0.2-3, 0.2-4 and 0.5-4 micrograms ml-1 for isocarboxazid, tranylcypromine sulphate and iproniazid phosphate, respectively. The second method involves the use of iodine monochloride (ICl) as an sigma-acceptor. It was found that ICl reacts quantitatively only with isocarboxazid and tranylcypromine sulphate; with iproniazid phosphate results were very poor. Beer's law is obeyed in the concentration range 2-20 micrograms ml-1 for both drugs. The optimum experimental parameters for colour production in each case were determined. The percentage recoveries obtained were in accordance with those obtained by the official methods. The proposed methods are characterized by high sensitivity.

Chlorides↗
PubMed2001

A possible indirect sympathomimetic action of metformin in the arterial vessel wall of spontanously hypertensive rats.

The antidiabetic drug metformin (MF) typically achieves only micromolar levels in plasma with normal therapeutic use. However, it is also known to accumulate in various tissues up to several times higher after standard oral dosing and we now have evidence from both in vivo and in vitro experiments with spontaneously hypertensive rats (SHR) that millimolar levels stimulate release of norepinephrine (NE) from vascular sympathetic nerve endings (SNEs). As shown in the present work with SHR tail arterial tissue (rich in SNEs), the known vasodilator effect of millimolar levels of MF on the smooth muscle (even if contracted with a nonadrenergic agonist), is attenuated by the presence of the SNEs unless phentolamine (an alpha receptor blocker) is present. We reasoned that the mechanism for this apparent NE-releasing action of MF is not exocytotic release as that would require depolarization of the neuronal cell membranes in SNEs, and MF at millimolar levels is known to repolarize (not depolarize) membranes of other cells. Thus, we tested the possibility that MF releases NE by an indirect sympathomimetic-like action. Such an action should be amplified by monoamine oxidase inhibitors (e.g. iproniazid) and blocked by NE-carrier inhibitors (e.g. desipramine). Accordingly, we found that the abovementioned attenuating effect of intact SNEs on MF's relaxation of SHR tail arterial tissue (compared to tissues in which SNEs were experimentally removed with 6-hydroxydopamine) was amplified nearly 3-fold by iproniazid (p<0.05) and blocked by desipramine (p<0.05). These results support an indirect sympathomimetic action of MF and raise the question whether commonly used antidepressants with properties similar to iproniazid and desipramine might alter MF's beneficial vasodilatory (and thus antihypertensive) effectiveness in diabetic patients with hypertension.

Animals↗
PubMed1979

Serum prolactin and brain and pituitary monoamine responses to chronic monoamine oxidase inhibition in the rat.

The acute administration of the monoamine oxidase inhibitor iproniazid to rats causes a highly significant suppression of serum prolactin levels at 2 h. At the same time there is a significant rise in the hypothalamic-median eminence concentrations of the biogenic monoamines dopamine, noradrenaline and serotonin. When iproniazid is administered daily to rats for 4 days and the animals are examined on the fifth day brain noradrenaline and serotonin levels are elevated similarly to those seen after acute administration but dopamine concentration is near normal while serum prolactin is significantly elevated. This study thus demonstrates that a quite specific and unexpected change occurs in the regulation of hypothalamic-median eminence dopamine when iproniazid is administered chronically and provides an explanation of previous observations in human subjects where raised serum prolactin levels are observed after chronic therapy with monoamine oxidase inhibitors.

5-Hydroxytryptophan↗
PubMed1989

Examination of the paradoxical lack of responsiveness of the guinea-pig vas deferens to tyramine.

1. The isolated superfused vas deferens from the guinea-pig was more sensitive to the contractile action of noradrenaline than that from the rat. Tyramine had about 10% of the potency of noradrenaline on the rat vas deferens, but had no contractile activity on the guinea-pig vas deferens (potency less than 0.1% of noradrenaline). 2. The response of the guinea-pig vas deferens to noradrenaline was not affected by tyramine in a concentration that produced a clear contractile response of the rat vas deferens. 3. Noradrenaline and tyramine released less radioactivity from guinea-pig than from rat vasa deferentia in which noradrenergic transmitter stores had been labelled with 3H-noradrenaline. In vasa deferentia from either species, tyramine released less radioactivity than noradrenaline. 4. Pretreatment with the monoamine oxidase inhibitor iproniazid increased the amount of radioactivity released by tyramine from vasa deferentia of both species, increased the contractile response of the rat vas deferens to tyramine, and resulted in the appearance of a contractile response to tyramine in the guinea-pig vas deferens. 5. alpha-methyltyramine, which is not a substrate for monoamine oxidase, had about the same potency as tyramine in releasing radioactivity from vasa deferentia of both species, and in contracting the rat vas deferens, but was virtually without contractile activity on the guinea-pig vas deferens. 6. Pretreatment with iproniazid resulted in the appearance of a contractile response to alpha-methyltyramine in the guinea-pig vas deferens. 7. Pretreatment with iproniazid resulted in change in the composition of the radioactivity released by tyramine, with an increase in the proportion of noradrenaline and a decrease in the proportion of deaminated products. There was also an increase in the amount of endogenous noradrenaline released by tyramine. 8. It was concluded that the main factor accounting for the lack of reactivity of the guinea-pig vas deferens to tyramine is intraneuronal metabolism of the noradrenaline displaced by it.

Amphetamines↗
PubMed1959

Increase of 5-hydroxytryptamine in the rat brain by raunescine.

The Rauwolfia alkaloid raunescine (5 mg./kg., intraperitoneally) increased the concentration of 5-hydroxytryptamine in the brains of rats after iproniazid pre-treatment. This was evident 3 to 4 hr. after raunescine administration. There was no general increase in the noradrenaline content of the brains. In the intestine, raunescine depleted the 5-hydroxytryptamine content by about 50% within 3 to 4 hr. if the animals had been pre-treated with iproniazid. Iproniazid did not increase the content of noradrenaline in the intestine.

Animals↗
PubMed1960

The effect of enzyme inhibitors on histamine catabolism in man.

The catabolism of histamine was studied in three female psychiatric patients by analysis of the [(14)C]-labelled metabolic products occurring in the urine after a subcutaneous injection of [(14)C]histamine. Each patient was studied before and during treatment with aminoguanidine or iproniazid.Without treatment the patients had a normal histamine catabolism. Aminoguanidine and iproniazid inhibited the oxidation of histamine to imidazoleacetic acid; iproniazid produed a 50% inhibition of the oxidation of methylhistamine to methylimidazoleacetic acid. After iproniazid a large proportion of the injected [C(14)]histamine was excreted as methyl [(14)C]histamine.

Amine Oxidase (Copper-Containing)↗
PubMed1978

Enhancement of platelet aggregation by tranylcypromine in mouse cerebral microvessels.

Tranylcypromine, given intraperitoneally at doses greater than or equal to 10 mg/kg, enhanced platelet aggregation in the arterioles on the cerebral surface in mice. Tranylcypromine inhibits prostacyclin synthesis in vitro. Iproniazid, which inhibits monoamine oxidase but not prostacyclin synthesis, failed to enhance platelet aggregation. The failure of iproniazid to enhance aggregation in this study rules out an effect on monoamine oxidase as the cause of tranylcypromine's action. That iproniazid inhibited aggregation indicates it has an effect opposite to that of tranylcypromine. Imidazole, a drug known to inhibit synthesis of both prostacyclin and thromboxane, failed to affect platelet aggregation. All of our data are compatible with the hypothesis that prostacyclin is an inhibitor of platelet aggregation. This hypothesis has been based largely on in vitro data, to which we now add in vivo support.

Animals↗
PubMedDate not supplied

[Importance of the initial monoamine oxidase activity for the development of the activating or inhibiting action of indolylhydrazides].

Effects of beta-(2-methyl indolyl-3) propionic acid hydrazide and alpha-butyl-beta-(2-methyl-5-carboxy indolyl-3) propionic acid hydrazide on the activity of monoamine oxidase were studied in rat brain in vitro. The compounds activated distinctly serotonin deamination under conditions of the enzyme inhibition, caused by pretreatment with iproniazide. The activation occurred only in the samples, which were not inhibited with iproniazide. The treatment with iproniazide prevented any alterations in content of amines, caused by the compounds in the rat brain in vivo.

Animals↗
PubMedDate not supplied

[Change in the concentration of free amino acids in the brain upon exposure to amnesia producing agents].

A comparison was made of free aminoacids content in the brain of rats after amnesia induced by an electric shock or an injection of iproniazid. Immediately after the electric shock the cystine content rises and there is a drop in the content of aspartic acid, proline and isoleucine. Twenty four hours later the content of most of the amino acids rises. A correlation has been found between the glycine content in the brain and the degree of amnesia. Under the influence of iproniazid the content of aspartic and glutamic acids, alanine, tyrosine and phenylalanine in the brain drops and that of proline, glycine, cystine and valine rises. It is assumed that the differences between the content of free aminoacids in the brain after electric shock and iproniazid reflect those between the mechanisms of amnestic action of the two agents.

Amino Acids↗
PubMedDate not supplied

[Importance of initial monoamine oxidase activity to the development of the activating or inhibitory effect of N-methyl- and N-ethyloctahydronaphthoazepines].

Effect of N-methyl- and N-ethyl octahydronaphthazepines upon the MAO activity of brain mitochondria of intact rats and brain homogenates of the animals treated with iproniazid has been investigated in vitro. These compounds (0.1 mumole/ml) stimulated the deamination of noradrenaline in samples with low initial enzymatic activity and inhibited it in samples having high initial enzymatic activity. The MAO activating effect of N-methyl octahydronaphthazepines in the brain homogenates occurred when the enzymatic activity was previously inhibited with iproniazid. In the homogenates, which were not pretreated with iproniazid, the activating effect was observed only in some cases.

Animals↗
PubMed1983

Effects of central monoamine compounds on tranylcypromine-induced barbital-withdrawal convulsions.

Challenge with tranylcypromine (Tcp) during barbital (B) withdrawal induces dose-related clonic-tonic convulsion (C-TC), which is also related to the severity of withdrawal signs and their changes with the passage of time. The effects of neuropharmacological agents on the Tcp-induced convulsions were observed. dl-Propranolol, phentolamine, phenoxybenzamine and methysergide had been administered intraperitoneally 20 approximately 30 minutes before Tcp challenge. B-withdrawn rats had been pretreated with alpha-methyl-p-tyrosine, 5-hydroxytryptophan, p-chlorophenylalanine or reserpine, or with the combination of iproniazid and reserpine (5 hrs after iproniazid administration) before Tcp challenge. alpha-MT and dl-propranolol inhibited B withdrawal convulsion markedly, though high doses of dl-propranolol rather tended to show a less effect on the convulsion. alpha-Adrenoceptor blockers scarcely inhibited the convulsion. Methysergide or 5-HTP failed to inhibit, but PCPA intensified the convulsion. Reserpine, when administered alone, aggravated the convulsion, but when administered after iproniazid, inhibited it significantly. These findings suggested that the balance between the activities of noradrenergic and serotonergic neurons might be of importance in the manifestation of B withdrawal convulsions, the former probably being excitatory and the latter, inhibitory.

Animals↗
PubMed1964

EFFECTS OF CHLORPROMAZINE AND BROMOLYSERGIC ACID DIETHYLAMIDE ON GASTRIC SECRETION OF ACID INDUCED BY HISTAMINE IN RATS.

In anaesthetized rats in which the lumen of the stomach was perfused with 0.001 to 0.00025 N-sodium hydroxide solution and the pH of effluent fluid was recorded continuously, intravenous administration of chlorpromazine caused transient inhibition of acid secretion. After acid secretion had returned to the control level the responses to histamine were greater than those before chlorpromazine was given. Aminoguanidine, iproniazid and bromolysergic acid diethylamide also potentiated the effect of histamine on acid secretion but the initial inhibition was absent. Indirect evidence from experiments in which mixtures of aminoguanidine with chlorpromazine or bromolysergic acid diethylamide and of iproniazid with chlorpromazine or bromolysergic acid diethylamide were given, suggests that chlorpromazine and bromolysergic acid diethylamide enhance responses to histamine by inhibition of imidazole-N-methyl transferase.

Amine Oxidase (Copper-Containing)↗
PubMedDate not supplied

Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.

A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Catabolism of 5-aminolevulinic acid to CO2 by rat liver mitochondria.

5-Aminolevulinic acid (ALA), the heme precursor accumulated in plasma and several organs of carriers of acute intermittent porphyria, hereditary tyrosinemia, and saturnism, was previously shown to yield reactive oxygen species upon metal-catalyzed aerobic oxidation and to cause the in vivo and in vitro impairment of rat liver mitochondrial functions. We have studied the uptake and catabolism of [5-14C]ALA to CO2 by isolated rat liver mitochondria (RLM) with the aim of determining whether possible ALA-driven oxidative injury to mitochondria can also occur into the matrix. Using silicone oil centrifugation of [5-14C]ALA-treated RLM, ALA was found to partition evenly into the intra- and extramatrix space of the mitochondrial preparations. The yield of evolved 14CO2 is very low (0.2%), responds to the concentration of added ADP, and is inhibited by malonate (75% at 2 mM), iproniazid (45% at 2 mM), beta-chloroalanine (36% at 1 mM), and aminooxyacetate (55% at 0.1 mM). With both iproniazid and aminooxyacetate, the percentage of inhibition is the same as that observed with the latter inhibitor alone. These data indicate that ALA decarboxylation by the Krebs cycle is a minor process and that it is initiated enzymically (transaminase) and not by metal-catalyzed ALA autoxidation.

Aminolevulinic Acid↗
PubMed1977

Behavioral withdrawal following several psychoactive drugs.

The chronic administration of several psychoactive drugs has been suggested to produce behavioral withdrawal syndromes in the absence of physical withdrawal. The present study employed four representative psychoactive drugs, amphetamine, chlorpromazine, iproniazid, and desipramine, in a common behavioral paradigm using electrical stimulation of the brain to test for behavioral withdrawal. Behavior differing from both predrug and drug produced behavior occurred following the termination of amphetamine, iproniazid and chlorpromazine administration. The first two drugs produced an increase in self stimulation during administration, followed by a very significant decrease after the drugs were discontinued. Chlorpromazine administration on the other hand, produced a decrease in self stimulation rates, followed by a rebound increase after termination of treatment. No systematic effects were observed with desipramine. The relationship between the behavioral effects of these drugs during and following treatment and possible homeostatic mechanism influencing response tendencies is discussed.

Animals↗
PubMed1978

Behavioral effects and metabolic fate of N,N-dimethyltryptamine in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), improniazid and chlorpromazine.

Behavioral aspects and metabolic fate of N,N-dimethyltryptamine (DMT) were studied in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), iproniazid or chlorpromazine (CPZ). DMT at doses of 2.5, 10.0, and 25.0 mg/kg produced several behavioral changes in a dose-related manner: inhibition of spontaneous locomotor movement, enhanced fright responses to sound stimuli, trembling, head twitching, inco-ordinated movements of hind-legs, flat or extended tail and abnormal posture with the extension of hind-legs. Pretreatment with ipromazid (153 mg/kg; 4 hr) but not SKF 525-A (50 mg/kg; 1 hr) prolonged the behavioral effects produced by 2.5 mg/kg DMT while CPZ (15 mg/kg; 0.5 hr) completely abolished the responses induced by 25 mg/kg DMT. Earlier behavioral effects generally coincided with the brain concentrations of DMT. Dose-dependent increases with rapid uptake and disappearance in the brain, plasma and hepatic levels of DMT were measured with doses of 10 and 25 mg/kg DMT. Iproniazid but not SKF 525-A markedly enhanced tissue levels of DMT. it is concluded that DMT is metabolized chiefly by monoamine oxidase rather than by drug-metabolizing hepatic microsomal enzymes and that DMT-induced behavioral effects are due to the parent compound rather than its metabolite.

Animals↗