Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Harmine”

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 19 recordsLinked to original sources
PubMed1987

Estimation of harmine and its derivatives by HPLC: correlation of brain harmine levels with jumping behavior in rats.

Brain harmine was simply and sensitively determined by high performance liquid chromatography (HPLC), and the relationship between brain harmine concentrations and the jumping behavior induced by harmine and apomorphine was investigated. The concentration of harmine and the peak height in HPLC showed a good correlation, and the detection limit was 0.05 pmole harmine. In rats treated with 2, 5 and 10 mg/kg of harmine, the concentrations of harmine in the brain cortex were 9.0, 21.3 and 43.1 nmole/g tissue (wet wt.), respectively. The regional brain harmine concentrations and the jumping activity measuring by a scoring system increased with increasing doses of harmine administered, and there was a direct relation between the harmine concentrations and the jumping activity. This relation was observed in washed membranes in which about 40% of the harmine in whole homogenate was present. Tissue subfractionation showed that 30% of the harmine in whole brain homogenates was in the P2 fraction, and of this, 70% was located in the synaptosomes. The brain homogenate did not metabolize harmine and no metabolite was detected in the brain 10 min after treatment with harmine and apomorphine. These results suggest that harmine itself, but not its metabolites, may be responsible for inducing the jumping behavior and that the jumping activity is correlated with brain harmine concentrations.

Alkaloids↗
PubMedDate not supplied

Metabolism of the beta-carbolines, harmine and harmol, by liver microsomes from phenobarbitone- or 3-methylcholanthrene-treated mice. Identification and quantitation of two novel harmine metabolites.

This study extends an investigation of the metabolism of the beta-carbolines, harmine and harmol, by untreated, phenobarbitone-induced, or 3-methylcholanthrene (MC)-induced mouse liver microsomes to identify two MC-inducible metabolites of harmine and to quantitate their rates of formation using 3H-labeled substrate. An HPLC system was devised to separate harmine and its metabolites. The major metabolite with MC-induced microsomes was identified by mass spectroscopy and by NMR to be 6-hydroxy-7-methoxyharman and was produced at an initial reaction rate of 11 nmol/min/mg of microsomal protein (27-fold induction). The other novel metabolite, 3- or 4-hydroxy-7-methoxyharman (the position of the hydroxyl group could not be definitively assigned by NMR) was produced at an initial reaction rate of 3.8 nmol/min/mg of microsomal protein (32-fold induction) which was similar to the rate of formation of the other metabolite, harmol, determined previously. All three metabolites were further metabolized to unidentified metabolites. Protein binding of [3H]harmine and [3H]harmol was measured and shown to be metabolism dependent. It was also noted that the alkali conditions used for optimal extraction stimulated the protein binding.

Alkaloids↗
PubMed1981

The effect of harmine on the action potential of the guinea-pig atrial muscle depends on the external calcium concentration.

1 The influence of the external calcium concentration on the effect of harmine 2 x 10(-5) M upon the guinea-pig atrial muscle was analysed. Transmembrane potentials of contractile fibres were measured during exposure to the drug at 30 degrees C. 2 In preparations superfused with 1.35 mM Ca2+-Tyrode solution and driven at 60/min (1 Hz) harmine depressed the amplitude of the action potential (AP) and the maximum velocity of the upstroke (dV/dt). The resting potential was not affected. Harmine depressed similarly the dV/dt of fibres superfused with 2.7 mM Ca2+-Tyrode solution but the AP was slightly enhanced. 3 Harmine diminished both the AP and the dV/dt of fibres superfused with 2.7 mM Ca2+-Tyrode solution and driven at a fast rate (180/min, 3 Hz). Increased external calcium concentration (5.4 mM) annulled the depressant effect on Ap while the action on dV/dt persisted. 4 It is concluded that the effect of harmine on the Ap depends on the external calcium concentration. Increase [Ca2+]o reverses the depressant effect of harmine because it annuls the effect of the drug on the slow component of the upstroke. The action on the initial fast component of the rising phase of the action potential persists.

Action Potentials↗
PubMed1985

Harmine-, LON-954- and 5-hydroxytryptophan-induced tremors in rats withdrawn from ethanol.

The tremors induced by harmine, LON-954 (N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride) and 5-hydroxytryptophan (5-HTP) were studied in control rats and in rats withdrawn for 16-48 hrs from 6 to 9 days' ethanol administration. The frequencies and the intensities of the tremors were determined electronically. In control rats the frequency spectra of the tremors induced by harmine (20 mg/kg) and LON-954 (10 mg/kg) showed a narrow peak frequency at about 10 Hz. Atropine (1.2 mg/kg) altered neither the frequency nor the intensity of these tremors. 5-HTP (50 mg/kg) when given 3.5 hrs after iproniazid (100 mg/kg) induced tremor with peak frequencies at 6-7 Hz and 12 Hz. In ethanol-withdrawn rats treated with harmine or LON-954 the frequency analysis of tremor revealed a narrow peak frequency at about 12 Hz, which was neither the characteristic frequency of ethanol withdrawal tremor (6 Hz) nor that of harmine or LON-954 (10 Hz). The intensity of both harmine- and LON-954-induced tremor was significantly increased in ethanol-withdrawn rats. The ethanol-withdrawn rats were markedly sensitized to the effect of iproniazid+ 5-HTP, shown by deaths. The peak frequencies of this tremor were the same as those in control rats. The results suggest that harmine-induced tremor involves a dopaminergic-5-HT'ergic imbalance and the tremor induced by LON-954 a dopaminergic-cholinergic imbalance in the brain. The tremor in ethanol-withdrawn rats seems to be mediated by alterations in the activity of the cerebral 5-HT'ergic system.

5-Hydroxytryptophan↗
PubMed1977

Harmine action in rats with lymphostatic encephalopathy.

In rats with lymphostatic encephalopathy the duration of harmine tremor was lengthened, and the brain concentrations of harmine decreased more slowly than in sham-operated controls. The tremor began simultaneously in both rat groups at coinciding brain concentrations of harmine. In rats with lymphostatic encephalopathy harmine concentrations in brain at the termination of tremor lay in the same range as in sham-operated controls. The plasma concentrations of harmine were not changed by the disease. It is concluded that during lymphostatic encephalopathy the lymphatic drug elimination from brain is impaired whereas--at least for harmine--the blood-brain barrier functions as normal.

Alkaloids↗
PubMed1994

Different effects of harmine on plasma concentrations of L-dopa and on cerebral dopamine metabolism in rabbits and rats.

The effects of short-term intravenous administration of harmine, a monoamine oxidase inhibitor, on the plasma concentrations of L-Dopa and on dopamine levels in the brain striata of rats and rabbits after L-Dopa administration were studied. Harmine affects the L-Dopa plasma concentrations in rabbits but not in rats: in fact in the former species the area under the concentration-time curve observed after administration of L-Dopa alone increased significantly when animals were pretreated with harmine. Dopamine striatal levels increased in concert with plasma L-Dopa concentrations after administration of L-Dopa in rats and rabbits. However pretreatment with harmine resulted in a significant increase of dopamine levels in the brain striata of rabbits only. These results suggest that harmine or one of its metabolites affect the brain dopamine system not merely as a type A monoamine oxidase inhibitor but with a modulatory effect, without a precise indication of site or mode of action of harmine.

Animals↗
PubMed1981

Pharmacological characteristics of abnormal behavior induced by harmine with special reference to tremor in mice.

Harmine, a hallucinogen with potent monoamine oxidase inhibitory properties, induced abnormal behavior, including tremor, scratching, head twitch and cage biting, in the mouse. A dose-dependent tremor was produced by all routes of administration of harmine. Although oxotremorine tremor was markedly suppressed by atropine, harmine tremor was unaffected by cholinergic drugs, remarkably inhibited by dopaminergic drugs, antidepressants and diazepam, mildly diminished by p-chlorophenylalanine, markedly augmented by 5-hydroxytryptophan and mildly increased by alpha-methyl-p-tyrosine. These findings suggest that a catecholaminergic (particularly dopaminergic) and serotonergic system imbalance plays an important role in the manifestation of harmine tremor. In view of these characteristics, harmine tremor may be useful as an effective experimental model for the evaluation of antiparkinsonism drugs, along with oxotremorine tremor because of the different mechanism of occurrence. In addition, harmine tremor appears to be useful in characterizing the properties of antidepressant drugs.

5-Hydroxytryptophan↗
PubMed1981

Role of brain monoamine systems in the jumping behavior induced in rats by the combination of harmine and apomorphine.

The role of brain monoamine systems in the jumping behavior induced by the combination of harmine and apomorphine was studied by using a MT pick-up to assess jumping behavior in rats. The jumping induced by the combination of harmine 10 mg/kg and apomorphine 2 mg/kg was enhanced by pretreatment with p-chlorophenylalanine, methysergide and by treatment with clonidine, while, it was reduced by pretreatment with 5-hydroxytryptophan, haloperidol, perphenazine, atropine and pilocarpine. The combination of harmaline or harmane and apomorphine also induced jumping with the aid of p-chlorophenylalanine. The combination of benserazide, L-DOPA and harmine induced jumping similar to that induced by harmine and apomorphine. Despite pretreatment with p-chlorophenylalanine the combination of apomorphine and benzylhydrazine, iproniazid, tranylcypromine or pargyline failed to induce jumping. These results suggest that this jumping behavior is induced not by the monoamine oxidase inhibitory effect of harmine but probably by the specific central action of harmine and on condition that the dopaminergic system is activated. The activation of this system appears to be essential, the noradrenergic system plays a facilitatory role, the serotonergic system an inhibitory role and the cholinergic system probably a specific role.

Alkaloids↗
PubMed1995

[Radioprotective effect of gamma-harmine and its carboline analogues].

gamma-Harmine (I), harmine (II) and harmaline (III) were isolated from Peganum harmala L. (Zygophylaceae). Tests were conducted with mice to detect whether gamma-harmine (a new compound), harmine, harmol (IV) and harmalol (V) are effective radioprotective compounds against gamma-ray irradiation. Intraperitoneal injection of the hydrochlorides of the four alkaloids 50-80 mg.kg-1 X 1 in NIH male mice 30-45 minutes before 8.6-9.7 Gy whole body 60Co irradiation significantly increased the survival effects (1.33-2.61) and 30-day survival survival rate in comparison with control mice. The results indicate that gamma-harmine exhibited relatively good radioprotective effect. gamma-harmine is the first alkaloid isolated from a plant having protective effects against whole-body lethal irradiation in mice.

Animals↗
PubMed1997

11C-harmine as a tracer for monoamine oxidase A (MAO-A): in vitro and in vivo studies.

Frozen-section autoradiography in rat brain sections as well as in vivo positron emission tomography (PET) studies in monkey brain were used for the determination of binding characteristics of O-[methyl-11C]harmine in an attempt to validate this ligand for the assessment of monoamine oxidase A (MAO-A). In frozen sections, the binding of [11C]harmine showed an apparent KD of the binding of 2 nM. The specific binding was inhibited by nanomolar concentrations of clorgyline, esuprone, brofaromine, and Ro 41-1049. The in vivo kinetic pattern in the monkey brain indicated a significant trapping, which was inhibited by pretreatment with clorgyline, moclobemide, or harmine. Different approaches for a quantitative determination of MAO-A enzyme binding were attempted and demonstrated an IC50 dose of harmine in the range of 0.05-0.1 mg/kg. The studies give strong indications for the validity of [11C]harmine as an in vivo tracer for the assessment of MAO-A enzyme binding in the brain.

Animals↗
PubMedDate not supplied

The effect of aprotinin on the harmine-induced tremor in lymphostatic encephalopathic and normal rats.

In normal and lymphostatic encephalopathic rats, aprotinin pretreatment alters the duration of the harmine tremor and the cerebral concentration of the alkaloid; low doses shorten the tremor and decrease the concentration, a high dose causes the opposite. Aprotinin may decrease or increase the blood-brain barrier permeability of harmine. Because the findings are similar in both groups of rats the blood-brain barrier for harmine is assumed to be intact in lymphostatic encephalopathy. However, sick rats possibly suffer from an impaired cerebral elimination of harmine.

Alkaloids↗
PubMed1976

Effect of harmine and brain lesions on apomorphine induced motor activity.

Application of harmine (10 mg/kg IP) 30 min before apomorphine decreased the motoric effects of the latter. Following harmine an increase in 5-HT and a decrease in 5-HIAA in different brain regions have been found. Injection of 5,6-DHT into nucleus medianus raphe 7 days before the experiment caused a significant increase of the apomorphine effect. Harmine pretreatment reduced this escessive motility as well as additional lesion of the substantia nigra with 6-OH-DA. Lesion induced by 6-OH-DA alone was without significant effect on the hypermotility following apomorphine. Application of PCPA 3 days before testing elicited an increase of apomorphine-induced hypermotolity which could be abolished by preceding harmine application. The experiments demonstrate the inhibitory effect of the central serotoninergic system on the apomorphine syndrome as well as the serotoninergic-dopaminergic interaction in hypermotility.

5,6-Dihydroxytryptamine↗
PubMed1980

Effects of harmine on transmembrane potentials of guinea-pig atrial muscle.

1 The effects of harmine 8.3 X 10(-5) M on membrane potentials of guinea-pig atrial muscle were analyzed and compared with those of harmaline. Transmembrane potentials of contractile fibres were measured during exposure to the drug at 30 degrees C. 2 In preparations superfused with 5.4 mmol K+-Tyrode, harmine produced a progressive reduction in the amplitude of the action potential (AP), in the absence of any change in resting potential (RP) and a prolongation of the duration of the action potential (APD). 3 Harmaline produced an enhancement of AP; RP was not affected and APD was prolonged. 4 The amplitude of slow responses elicited by noradrenaline in 16.2 mmol K+-Tyrode was enhanced by harmine. 5 It is proposed that dehydrogenation of harmaline to harmine reverses the initial stimulatory action of harmaline on AP because the depressant action on the fast component of the upstroke prevails over the stimulatory effect on the slow component.

Action Potentials↗
PubMed1994

Pharmacological evaluation of alcohol withdrawal-induced inhibition of exploratory behaviour and supersensitivity to harmine-induced tremor.

Rats given a liquid diet containing 10% (v/v) alcohol consume high quantities of alcohol. Within 8 hr after cessation of the alcohol intake, the animals will show alcohol-withdrawal reactions including a supersensitivity to harmine-induced tremor and an inhibition of exploratory behaviour in a neutral environment. Several drugs can overcome one or more of these alcohol-withdrawal reactions. A reduction of the alcohol withdrawal-induced inhibition of exploration, in terms of both the number of transits into the open field and the time spent in the open field, was obtained with chlordiazepoxide, ritanserin, mianserin and propranolol. Of these four compounds, propranolol and mianserin were also active against the supersensitivity to both 5.00 and 10.00 mg/kg harmine-induced tremor. Chlordiazepoxide and ritanserin were only active against 5.00 mg/kg harmine. Other compounds that reversed the supersensitivity to harmine-induced tremor during alcohol withdrawal included buspirone, fluoxetine, haloperidol, clonidine, flunarizine and baclofen. Very limited effects on both alcohol-withdrawal reactions were observed with ondansetron, nimodipine and MK-801. Risperidone and SCH 23390 were inactive. These results demonstrate that some alcohol withdrawal reactions can be studied in a systematic way and that various pharmacological agents can differentially interact with these alcohol withdrawal reactions.

Alcohol Withdrawal Delirium↗
PubMed1979

Modification by levo-propranolol of tremors induced by harmine in mice.

It has been recently reported that the levo isomer of propranolol possesses anti-serotonin properties in animals. Since harmine-induced behavioural changes in mice are reported to be mediated through central serotonergic receptors, an attempt was made to test whether 1-propranolol would also modify harmine-induced responses by virtue of its anti-serotonergic or anti-adrenergic property. The results indicated that l- and dl-propranolol inhibited central serotonin receptor mediated responses to harmine in mice, a finding that is analogous to other recent observations.

Animals↗
PubMed1975

Studies of the interaction of the fluorophores harmine and harmaline with calf thymus DNA.

The binding to calf thymus DNA of the hallucinogen harmine and one of its analogues harmaline was studied by absorption spectrophotometry and fluorescence quenching analysis. Viscosity measurements were also carried out. For both molecules, quenched and unquenched sites on DNA are present. For each type of binding site, the value of the product of the number of sites times the association constant was determined. Harmine is more strongly bound than harmaline. Viscosity measurements indicate intercalation in the case of harmine only.

Alkaloids↗
PubMed1980

Frequency dependence of the effect of harmine on the duration of the action potential of guinea pig atrial muscle.

The effect of harmine on the duration of the action potential (APD) of guinea pig atrial muscle is analyzed. Harmine prolongs APD through both a depressant effect on automaticity and a direct effect on atrial repolarization. In atria driven at a constant rate: (a) the direct effect becomes less with a faster drive; (b) an increase in concentration of harmine does not result in a greater prolongation of APD. Increased extracellular Ca2+ concentration annulles the APD-prolonging effect.

Action Potentials↗
PubMed1986

Harmine reverses the inhibition of lordosis by the 5-HT2 antagonists pirenperone and ketanserin in the female rat.

The beta-carboline harmine was found to facilitate lordosis behavior in ovariectomized rats primed with estradiol benzoate. Moreover, harmine reversed the inhibition of lordosis by the serotonin type 2 (5-HT2) antagonists pirenperone and ketanserin in rats primed with estradiol benzoate and progesterone. These results suggest that harmine facilitates lordosis by enhancing activity at 5-HT2 receptors.

Alkaloids↗