Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Clorgyline”

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
PubMed2002

Strategy for the formation of parametric images under conditions of low injected radioactivity applied to PET studies with the irreversible monoamine oxidase A tracers [11C]clorgyline and deuterium-substituted [11C]clorgyline.

The construction of parametric positron emission tomography images of enzyme or receptor concentration obtained using irreversibly binding radiotracers presents problems not usually encountered with reversibly binding radiotracers. Difficulties are most apparent in brain regions having low blood flow and/or high enzyme or receptor concentration and are exacerbated with noisy data. This is especially true when minimal doses of radiotracer are administered. A comparison was recently reported of the irreversible monoamine oxidase A (MAO A) radiotracers [11C]clorgyline (CLG) and deuterium-substituted [11C]clorgyline (CLG-D) in the human brain using region of interest (ROI) analysis in which the authors observed an unexpected loss of image contrast with CLG-D compared with CLG. In order to more fully investigate patterns of binding of these irreversibly binding radiotracers, a strategy was devised to reduce noise in the generation of parametric images of the model term related to enzyme or receptor concentration. The generalized linear least squares (GLLS) method of Feng et al. (1995), a rapid linear method that is unbiased, was used for image-wide parameter estimation. Since GLLS can fail in the presence of large amounts of noise, local voxels were grouped within the image to increase the signal, and the GLLS method was combined with the standard nonlinear estimation methods when necessary. Voxels were grouped together depending on their proximity and whether they fell within a specified range of the time-integrated image. It was assumed that voxels meeting both criteria are functionally related. Simulations reflecting varying enzyme concentrations were performed to assess precision and accuracy of parameter estimates in the presence of varying amounts of noise. Using this approach, images were generated of the combination parameter lambdak3 (lambda = K1/k2, where K1 and k2 are plasma-to-tissue and tissue-to-plasma transport constants, respectively) that is related to enzyme concentration as well as images of the transport constant K1 for individual subjects. Reasonably high-quality images of both K1 and lambdak3 were obtained for CLG and CLG-D for individual subjects even with low injected doses averaging 6 mCi. While there were no differences in the K1 images, the lambdak3 images revealed the loss of contrast previously reported for CLG-D using the ROI analysis. This method should be generalizable to other tracers and should facilitate the analysis of group differences.

Brain↗
PubMed2006

Differential effects of clorgyline on sensitization to quinpirole in rats tested in small and large environments.

RATIONALE: Cotreatment with clorgyline shifts the development of sensitization to the D2/D3 dopamine receptor agonist quinpirole from locomotion to mouthing, an effect apparently unrelated to the monoamine oxidase inhibition property of clorgyline. This phenomenon was demonstrated in rats examined in small activity chambers. However, like with other psychostimulant drugs, sensitization to quinpirole is modulated by environmental context. It is not known whether the clorgyline cotreatment effect is likewise influenced by the environment. OBJECTIVE: To determine the generality of the clorgyline effect on behavioral sensitization by evaluating the effects of clorgyline cotreatment on sensitization to quinpirole in two different environments: a small activity chamber and a large open field. METHODS: Male rats received eight injections of quinpirole (0.5 mg/kg, twice weekly) in an open field or activity chamber; one group in each environment received a constant infusion of clorgyline (1 mg/kg/day via osmotic minipumps) while the other group served as the sham surgery control. For quinpirole injection 7 or 8, rats were tested in the alternate environment. RESULTS: In activity chambers, clorgyline cotreatment switched sensitization to quinpirole from locomotion to mouthing. In the open field, clorgyline cotreatment increased mouthing and expanded the explored space without a change in path stereotypy or the amount of locomotion compared to treatment with quinpirole alone. CONCLUSIONS: Structure of the environment can modulate the clorgyline cotreatment effect on behavioral sensitization to quinpirole. The behavioral profiles produced by clorgyline cotreatment in the two environments resembled the behavioral effects observed with quinpirole and D1 agonist cotreatment. It is suggested that clorgyline cotreatment produces a behavioral profile characteristic of enhanced dopamine D1 and D2 receptor costimulation.

Animals↗
PubMed2001

Non-MAO A binding of clorgyline in white matter in human brain.

Clorgyline is an irreversible inhibitor of monoamine oxidase (MAO A) which has been labeled with carbon-11 (C-11) and used to measure human brain MAO A with positron emission tomography (PET). In this study we compared [11C]clorgyline and deuterium-substituted [11C]clorgyline ([11C]clorgyline-D2) to better understand the molecular link between [11C]clorgyline binding and MAO A. In PET studies of five normal healthy volunteers scanned with [11C]clorgyline and [11C]clorgyline-D2 2 h apart, deuterium substitution generally produced the expected reductions in the brain uptake of [11C]clorgyline. However, the reduction was not uniform with the C-11 binding in white matter being significantly less sensitive to deuterium substitution than other brain regions. The percentages of the total binding attributable to MAO A is largest for the thalamus and smallest for the white matter and this is clearly seen in PET images with [11C]clorgyline-D2. Thus deuterium-substituted [11C]clorgyline selectively reduces the MAO A binding component of clorgyline in the human brain revealing non-MAO A binding which is most apparent in the white matter. The characterization of the non-MAO A binding component of this widely used MAO A inhibitor merits further investigation.

Adult↗
PubMed2003

Clorgyline-induced switch from locomotion to mouthing in sensitization to the dopamine D2/D3 agonist quinpirole in rats: role of sigma and imidazoline I2 receptors.

RATIONALE: The monoamine oxidase inhibitor (MAOI) clorgyline, blocks locomotor sensitization to the D(2)/D(3) dopamine agonist quinpirole and sensitizes self-directed mouthing behavior in rats by a mechanism independent of MAO inhibition. Clorgyline has a high affinity for imidazoline I(2) and sigma receptors, which could account for its effects on quinpirole sensitization. OBJECTIVES: To examine whether the effect of clorgyline on quinpirole sensitization is attributed to stimulation of either I(2) or sigma receptors. METHODS: In one experiment, rats received injections of the I(2) receptor agonist 2-BFI (0.2 mg/kg, IP) or vehicle, 90 min prior to each injection of quinpirole (0.5 mg/kg, SC, x 8, twice weekly) or saline. A similar protocol was used to examine the effects of the MAOI Ro 41-1049 (10 mg/kg, SC) on quinpirole sensitization. Unlike clorgyline, Ro 41-1049 has no affinity for sigma or I(2) sites. An initial experiment demonstrated that intermittent injections of clorgyline (1 mg/kg, SC) are as effective as a continuous clorgyline administration (1 mg/kg per day via osmotic mini-pump) on quinpirole sensitization. RESULTS: Like clorgyline, Ro 41-1049, but not 2-BFI, blocked the development of quinpirole-induced locomotor sensitization and induced instead sensitization of self-directed mouthing. CONCLUSIONS: Because Ro 41-1049 produced the same effects as clorgyline, and 2-BFI had no effects on quinpirole sensitization, it is unlikely that clorgyline exerts its effects via an action at sigma or I(2) receptors. Our results are consistent with the suggestion that clorgyline and Ro 41-1049 affect the behavioral response to quinpirole via the MAOI-displaceable quinpirole binding (MQB) site, and the hypothesis that the MQB site selects what motor output becomes sensitized to repeated injections of quinpirole.

Animals↗
PubMed1984

Differential effects of clorgyline on catecholamine and indoleamine metabolites in the cerebrospinal fluid of rhesus monkeys.

The effects of acute and chronic administration of clorgyline, an irreversible inhibitor of monoamine oxidase type A (MAO-A), on the deaminated metabolites of norepinephrine, dopamine and serotonin were examined in rhesus monkey cerebrospinal fluid (CSF). Acute clorgyline treatment resulted in highly significant, dose-dependent reductions in 3-methoxy-4-hydroxyphenylglycol (MHPG) of 50% (1 mg/kg) and 68% (2 mg/kg) compared to pretreatment values. Chronic clorgyline administration (0.25 to 0.5 mg/kg X 24 days) resulted in a 67% reduction in CSF MHPG. In contrast, the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were less affected by acute clorgyline administration, being reduced significantly only after the 2 mg/kg dose, which lowered 5-HIAA 27% and HVA 48%. Chronic clorgyline treatment had no significant effect on the CSF concentrations of HVA and 5-HIAA. These data, which suggest that MAO-A inhibition by clorgyline in vivo is more closely associated with changes in the noradrenergic than the serotonergic or dopaminergic systems in nonhuman primates, are in general agreement with the effects of clorgyline on CSF and urinary biogenic amine metabolites in man. They differ from several in vitro studies which indicate a primary role of MAO-A in the metabolism of serotonin and of MAO-B in norepinephrine degradation in primate brain. The discrepancies may reflect modulating effects of synaptic feedback mechanisms on the actions of clorgyline in vivo or perhaps a failure of CSF metabolites to adequately reflect brain amine metabolism changes. The lack of change in platelet MAO-B activity during clorgyline treatment together with the minimal changes in HVA concentrations indicate that the selective inhibitory effects of clorgyline on MAO-A were maintained during chronic administration of low drug doses.

Animals↗
PubMed1993

Chronic treatment with the monoamine oxidase inhibitors clorgyline and pargyline down-regulates non-adrenoceptor [3H]-idazoxan binding sites in the rat brain.

1. The binding of [3H]-idazoxan in the presence of 10(-6) M (-)-adrenaline was used to quantitate non-adrenoceptor idazoxan binding sites (NAIBS) in the rat brain after treatment with various psychotropic drugs. 2. Chronic treatment (14 days) with the monoamine oxidase (MAO) inhibitors clorgyline (0.3-10 mg kg-1, i.p.) and pargyline (10 mg kg-1, i.p.), but not with Ro 41-1049 (1 mg kg-1, i.p.), markedly decreased (30-50%) the density of NAIBS in the cerebral cortex without any apparent change in the affinity of the radioligand. 3. Acute (1 day) and/or chronic treatments (14 days) with other psychotropic drugs such as desipramine (3 mg kg-1, i.p.), cocaine (10 mg kg-1, i.p.), reserpine (0.12 mg kg-1, s.c.), haloperidol (1 mg kg-1, i.p.) and diazepam (10 mg kg-1, i.p.) did not alter the density of NAIBS in the cerebral cortex. 4. In vitro, the propargylamines clorgyline, pargyline and deprenyl displaced the binding of [3H]-idazoxan to NAIBS from two distinct sites, but only clorgyline displayed an apparent very high affinity for a relevant population of NAIBS (KiH = 40 pM; KiL = 10.6 microM). The structurally diverse MAO inhibitors Ro 16-6491 (selective for MAO-B) and Ro 41-1049 (selective for MAO-A), as well as the other psychotropic drugs (desipramine, cocaine, reserpine and haloperidol) displaced the binding of [3H]-idazoxan to NAIBS monophasically and with very low potencies. As expected, the MAO inhibitors clorgyline and Ro 41-1049 displaced the binding of [3H]-Ro 41-1049 to MAO-A monophasically and with high potencies (Ki values: 0.18 nM and 22 nM, respectively). In contrast, idazoxan displayed very low affinity (Ki =40 microM) against the binding of pH]-Ro 41-1049 to MAO-A. These results disprove a direct interaction between [3H]-idazoxan and the enzyme MAO.5. Preincubation of cortical membranes with clorgyline (10-9M or 10-6 M for 30 min) or pargyline(10-6 M or 10-5M for 30 min), reduced by 30-50% and by 17-30%, respectively, the total density of NAIBS without any apparent change in the affinity of the radioligand. Preincubation with 10-6M clorgyline did not alter the affinity of cirazoline for the two populations of NAIBS, but reduced by 60%the binding of [3H]-idazoxan to the high affinity site without affecting the binding of the radioligand to the low affinity site. These results indicate that the two MAO inhibitors irreversibly block the binding of[3H]-idazoxan to NAIBS.6. In vivo, however, various acute treatments with clorgyline (1-20 mg kg-1, i.p.) for different time intervals (6-48 h) did not alter the density of NAIBS. In vivo, only very high doses of clorgyline (40 and 80 mg kg-1, i.p.) induced modest decreases (21-28%) in the density of NAIBS in the cerebral cortex.7. Together the results indicate that the irreversible binding of clorgyline and pargyline to NAIBSfound in vitro does not fully explain the marked decreases in the density of NAIBS found in vivo after the chronic treatments. It is suggested that the down-regulation of NAIBS induced in vivo by clorgyline and pargyline, through a direct or indirect mechanism, may have functional implications.

Animals↗
PubMed2006

Modification of morphine-induced hyperlocomotion and antinociception in mice by clorgyline, a monoamine oxidase-A inhibitor.

We evaluated the effects of pretreatment with clorgyline, an irreversible monoamine oxidase (MAO)-A inhibitor, on morphine-induced hyperlocomotion and antinociception. A single administration of morphine (30 mg/kg, i.p.) to male ICR mice induced a hyperlocomotion. ANOVA analysis revealed the statistical significance of the morphine effect on horizontal locomotion and of the clorgyline pretreatment x morphine interaction effect, but not of the effect of clorgyline pretreatment. The initial (5 min after challenge) phase of morphine actions vs. saline challenge appeared as if morphine had a strong inhibitory effect on locomotor activity in combination with different doses of clorgyline. The mice administered with morphine in combination of clorgyline (1 and 10 mg/kg) did not show any stereotypic behaviors. Clorgyline at a dose of 0.1 mg/kg but not other doses tested significantly potentiated morphine-induced antinociception evaluated by tail flick but not hot plate test. During the measurements of locomotor activity and antinociception, clorgyline at doses of 1 and 10 mg/kg significantly inhibited monoamine metabolism through MAO. These results suggest that clorgyline showed an inhibitory effect on morphine-induced hyperlocomotion, but not antinociception, through MAO inhibition. There is not a possibility that clorgyline pretreatment enhanced morphine action on motor activity, resulting in the abnormal behavior from hyperlocomotion to stereotypic movements.

Analgesics↗
PubMed1994

Autonomic and behavioral thermoregulation in the golden hamster during subchronic administration of clorgyline.

Chronic administration of clorgyline, a type-A monoamine oxidase inhibitor, leads to a decrease in peritoneal (i.e., core) temperature of golden hamsters. To better understand the mechanisms of clorgyline's thermoregulatory effects, autonomic and behavioral thermoregulatory effectors were measured in Syrian hamsters following chronic infusion of clorgyline via a minipump (2 mg/kg/day). Metabolic rate, evaporative water loss, motor activity, and core temperature were measured after 60 min of exposure to ambient temperatures (Ta) of 5, 20, 30, and 35 degrees C. Behavioral thermoregulatory responses were assessed by measuring selected Ta and motor activity of the same animals in a temperature gradient over the course of 23 h. Metabolic rate and motor activity were significantly elevated in clorgyline-treated hamsters exposed to a Ta of 5 degrees C. There were no effects of clorgyline on evaporative water loss. In the temperature gradient the mean selected Ta of clorgyline-treated hamsters was nearly equal to that of the saline-treated hamsters, 30.7 and 31.2 degrees C, respectively. On the other hand, the mode of selected Ta in the clorgyline group was 2.8 degrees C higher than that of the saline group. Motor activity in the gradient was significantly elevated and food consumption was depressed by clorgyline treatment. Overall, these findings indicate that chronic clorgyline treatment in the golden hamster results in novel autonomic and behavioral modification; it stimulates metabolic thermogenesis during cold exposure, but appears to increase the behavioral zone of thermoneutrality. This latter effect may mean an improvement in heat tolerance, suggesting that this drug might assist in the adaptation to warm temperatures.

Animals↗
PubMed2004

Hypophysectomy does not block sensitization to the dopamine agonist quinpirole or its modulation by the MAOI clorgyline.

Repeated administration of the dopamine agonist quinpirole induces behavioral sensitization in rats that is characterized by a four- to eight-fold increase in the amount of locomotion compared to an acute dose of quinpirole, in the absence of any increases in mouthing behavior. The monoamine oxidase (MAO) inhibitor, clorgyline, switches behavioral sensitization to quinpirole from that of locomotion to self-directed mouthing. The mechanism by which clorgyline produces this switch in behavioral sensitization is unknown, but is independent of the known effects of clorgyline, namely, inhibition of MAO, inhibition of striatal dopamine uptake, or stimulation of sigma and I(2) receptors. Because clorgyline also inhibits hypothalamo-pituitary-adrenal (HPA) axis function, and increased HPA activity facilitates the behavioral effects of psychostimulant drugs, the effects of clorgyline on quinpirole sensitization are possibly due to an inhibition of HPA function. Therefore, the present study examined whether HPA activity is required for sensitization to quinpirole, and whether clorgyline exerts its effects on quinpirole sensitization via inhibition of HPA function. Control and hypophysectomized rats were administered clorgyline (1 mg/kg, s.c.) or vehicle 90 min before each injection of quinpirole (0.5 mg/kg x 8, twice weekly) or saline. To assess the level of sensitization reached by control and hypophysectomized rats, test injections of quinpirole (0.0, 0.07, and 0.2 mg/kg) were administered. Chronic quinpirole administration produced equivalent levels of locomotor sensitization in control and hypophysectomized rats. Clorgyline was equally effective in blocking the development of locomotor sensitization in control and hypophysectomized rats, and in sensitizing self-directed mouthing. The present study suggests that (1). HPA function is not necessary for the development of quinpirole sensitization and, (2). clorgyline does not produce its effects on behavioral sensitization to quinpirole via an inhibition of HPA activity. Moreover, the observation that quinpirole sensitization develops normally in the absence of any pituitary endocrine function suggests that pituitary-gonadal and pituitary-thyroid axes activity are also not necessary for quinpirole sensitization to occur.

Animals↗
PubMed1992

Effects of clorgyline on the release of noradrenaline from rat vas deferens.

Release of endogenous noradrenaline (NA) and functional activity of presynaptic alpha 2-adrenoceptors were measured in isolated rat vas deferens following acute (2 mg/kg) or chronic (21 * 1 mg/kg daily, i.p.) treatment with clorgyline. Noradrenaline tissue content was higher in rats treated chronically with clorgyline than in those treated acutely. In vitro experiments done in the presence of 1 microM desipramine and 0.5 microM yohimbine showed that NA release, elicited by electrical field stimulation, was higher in chronic clorgyline rats than in controls, while no significant difference was found between acute clorgyline and control rats. Yohimbine enhanced evoked release of NA in all treatment groups, provided that desipramine was present in the Krebs solution, and the enhancement was non significantly higher in chronic clorgyline than in acute clorgyline and control rats. Efflux of 3,4-dihydroxyphenylglycol was lower in chronic clorgyline rats than in other groups. No difference was found between the treatment groups in a 1 min [3H]NA uptake into the tissue, nor in the ability of desipramine (1 microM) to block the uptake. The results indicate that following chronic treatment with clorgyline, evoked release of NA increased, and there was no reduction in the ability of the presynaptic alpha 2-adrenoceptor inhibitory mechanism to reduce nerve stimulation induced release of NA.

Animals↗
PubMed2001

Species differences in [11C]clorgyline binding in brain.

[11C]Clorgyline selectively binds to MAO A in the human brain. This contrasts with a recent report that [11C]clorgyline (in contrast to other labeled MAO A inhibitors) is not retained in the rhesus monkey brain [4]. To explore this difference, we compared [11C]clorgyline in the baboon brain before and after clorgyline pretreatment and we also synthesized deuterium substituted [11C]clorgyline (and its nor-precursor) for comparison. [11C]Clorgyline was not retained in the baboon brain nor was it influenced by clorgyline pretreatment or by deuterium substitution, contrasting to results in humans. This suggests a species difference in the susceptibility of MAO A to inhibition by clorgyline and represents an unusual example of where the behavior of a radiotracer in the baboon brain does not predict its behavior in the human brain.

Animals↗
PubMed2000

Chronic clorgyline induces selective down-regulation of alpha2-adrenoceptor agonist binding sites in rat brain.

Inactivation of alpha2-adrenoceptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been shown to induce an increase in brain regulatory G alpha(i1/2) proteins, which was related to biphasic recovery of agonist binding sites. To investigate further the nature of this phenomenon, the chronic effects of clorgyline (a monoamine oxidase inhibitor antidepressant) on the recovery of alpha2-adrenoceptors after EEDQ and on EEDQ-induced up-regulation of G alpha(i1/2) proteins were assessed in rat brain. Clorgyline (1 mg kg(-1) for 7-35 days) induced a time-dependent down-regulation (20% to 55%) of the density of cortical alpha2-adrenoceptor agonist sites ([3H]UK 14304/bromoxidine binding) but not of antagonist sites ([3H]RX 821002/2-methoxy idazoxan binding). However, chronic clorgyline did not alter the immunoreactive levels of G alpha(i1/2), G alpha(i3), and G alpha(o) proteins in cortex. In clorgyline-treated rats, the turnover functions for agonist and antagonist binding sites (receptor recovery after EEDQ) were different and indicated that the reduced density of alpha2-adrenoceptor agonist sites induced by clorgyline was due to a greater rate of receptor disappearance. The recovery of [3H]UK 14304 binding in clorgyline-treated rats did not fit a biphasic recovery model and the turnover parameters were very similar to those obtained for the second phase of recovery (biphasic model) of agonist binding sites in naive rats. This suggested that clorgyline down-regulated only the alpha2-adrenoceptors of rapid turnover which is associated with the increases in the expression of G alpha(i1/2) proteins induced by EEDQ. In this context, clorgyline (1 mg kg(-1) for 7 days) fully prevented the up-regulation (50%) of brain G alpha(i1/2) proteins induced by EEDQ. The results indicate that one relevant mechanism involved in the in vivo desensitization of brain alpha2-adrenoceptors is an effective impairment of receptor-G protein coupling.

Adrenergic alpha-Agonists↗
PubMed1983

Effect of clorgyline (a MAO type A inhibitor) on locomotor activity in the Syrian hamster.

Syrian hamsters in a lighting schedule of 14 h of light per day (LD 14:10) and housed in cages equipped with running wheels exhibited a clear onset of locomotor activity during the 1st h after lights off. Implantation of osmotic minipumps containing clorgyline (2 mg . kg-1 . day-1), an irreversible inhibitor of monoamine oxidase type A, caused a 1.5-h delay in the onset of wheel running by the 7th day of treatment. Increasing dosages of clorgyline (0.5, 1, 2, or 4 mg . kg-1 . day-1) caused increasing delays. Hamsters shifted from LD 14:10 to LD 10:14 underwent a 3-h advance in the onset of wheel running. Animals treated with clorgyline (2 mg . kg-1 . day-1) exhibited a markedly slowed rate of advance in activity onset, which did not prevent the short photoperiod from inhibiting reproductive function. Additionally, removal of the pineal gland did not affect wheel-running onset and did not prevent the delay in activity onset during clorgyline treatment. Hamsters in LD 14:10 were "released" into constant darkness (DD) for 3 days to prevent masking of activity onsets and offsets by light. Delays in activity onset in LD 14:10 caused by clorgyline (2 mg . kg-1 . day-1) persisted when these animals were released into DD. Activity offset in LD 14:10 occurred at lights on before and during clorgyline treatment but was delayed when the treated animals were maintained in DD. Drug-induced delays in both activity onset and offset suggest that clorgyline is not simply shortening the duration of activity or changing the expression of activity relative to the light-dark cycle, but is delaying the phase position of the circadian rhythm in locomotor activity. Clorgyline may act directly on the central oscillatory mechanism that drives the rhythm.

Animals↗
PubMed2006

Methamphetamine reward in mice as assessed by conditioned place preference test with Supermex sensors: effect of subchronic clorgyline pretreatment.

Recent studies in our laboratory have shown that methamphetamine (METH)-induced hyperlocomotion and behavioral sensitization in mice were inhibited by clorgyline, an irreversible monoamine oxidase inhibitor. In this study, the effect of clorgyline pretreatment on METH-induced rewarding effect was assessed by a conditioned place preference (CPP) test, using an apparatus developed with Supermex sensors (infrared pyroelectric sensors). Although intact male ICR mice showed significant CPP for METH (0.5 mg/kg, i.p.), pretreatment with subchronic clorgyline (0.1 and 10 mg/kg, s.c.) did not affect the magnitude of CPP. At a dose of 1 mg/kg, pretreatment of the mice with clorgyline showed a similar CPP index in both saline/saline and METH/saline pairing groups. During the conditioning session, the mice did not express behavioral sensitization to METH. Pretreatment with clorgyline (0.1, 1, and 10 mg/kg) decreased striatal apparent monoamine turnover in a dose-dependent manner. These results indicated that clorgyline pretreatment (0.1 and 10 mg/kg) did not influence the METH-induced rewarding effect in mice, although pretreatment of the mice with clorgyline at a dose of 1 mg/kg appeared to influence the CPP for METH.

Analysis of Variance↗
PubMed2001

Acute and chronic effects of desipramine and clorgyline on alpha(2)-adrenoceptors regulating noradrenergic transmission in the rat brain: a dual-probe microdialysis study.

1. The effects of desipramine (3 mg kg(-1) i.p.) and clorgyline (1 mg kg(-1) i.p.) on extracellular noradrenaline (NA) in the locus coeruleus (LC) and cingulate cortex were assessed in freely-moving rats by dual-probe microdialysis. Functional activities of alpha(2)-adrenoceptors regulating NA release in the LC and cingulate cortex were determined by systemic (0.3 mg kg(-1) i.p.) or local (0.1 - 100 microM) clonidine administration. 2. Extracellular NA was increased in the LC and cingulate cortex following acute desipramine but not clorgyline treatment. Systemic clonidine decreased NA similarly in desipramine-, clorgyline-, and saline-treated animals, in both brain areas. 3. Long-term (twice daily, 14 days) but not short-term (twice daily, 7 days) desipramine, and long-term clorgyline (once daily, 21 days) treatments increased NA (3 fold) in cingulate cortex but not in the LC. Following long-term treatments, responses of NA to systemic clonidine were attenuated in the LC and cingulate cortex. 4. Clonidine perfusion by reverse dialysis into the cingulate cortex decreased local NA (-55 +/- 9%). The effect was attenuated by long-term desipramine (-31 +/- 9%) and clorgyline (-10 +/- 2%) treatments. 5. Clonidine perfusion by reverse dialysis into the LC decreased NA in the LC (-89 +/- 2%) and in cingulate cortex (-52 +/- 12%). This effect was attenuated in the LC following long-term desipramine (-72 +/- 4%) and clorgyline (-62 +/- 12%) treatments but it was not modified in the cingulate cortex (-57 +/- 10% and -68 +/- 6%, respectively). 6. These findings demonstrate that chronic desipramine or clorgyline treatments increase NA in noradrenergic terminal areas and desensitize alpha(2)-adrenoceptors modulating local NA release at somatodendritic and terminal levels. However, somatodendritic alpha(2)-adrenoceptors that control LC firing activity are not desensitized.

Adrenergic Uptake Inhibitors↗
PubMed1993

Acceleration by chronic treatment with clorgyline of the turnover of brain alpha 2-adrenoceptors in normotensive but not in spontaneously hypertensive rats.

1. The aim of this study was to quantitate and compare the turnover of alpha 2-adrenoceptors in the cerebral cortex of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, and its modulation during chronic treatment with the monoamine oxidase (MAO) inhibitor, clorgyline. 2. In SHR, the specific binding of the agonist [3H]-UK 14304 and of the antagonist [3H]-RX 821002 was significantly reduced in the brain (Bmax 15-19% lower) as compared to that in sex- and age-matched WKY rats. In contrast, no significant changes in the Kd values for both radioligands were found between WKY and SHR rats. Therefore, SHR rats offer a genetic model with a lower density of alpha 2-adrenoceptors in the brain. 3. Chronic treatment (21-35 days) with clorgyline (1 mg kg-1, i.p.) markedly decreased the density of brain alpha 2-adrenoceptors ([3H]-UK 14304 binding) in Sprague-Dawley (Bmax reduced by 50%) and in WKY (Bmax reduced by 30%) rats without any apparent change in the affinity of the radioligand. In contrast, the density of brain alpha 2-adrenoceptors in SHR was not down-regulated by chronic clorgyline treatment. 4. The recovery of [3H]-UK 14304 binding after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 1.6 mg kg-1) (an alkylating agent for the alpha 2-adrenoceptor) was assessed in control and clorgyline-treated (1 mg kg-1; i.p. for 7-21 days) WKY and SHR rats to study the process of alpha 2-adrenoceptor repopulation and to calculate receptor turnover parameters. 5. The simultaneous analysis of receptor recovery curves revealed that the turnover of brain alpha2-adrenoceptors in SHR rats was accelerated (k = 0.141 day-1;t 1/2= 4.9 days; r/k =40 fmol mg-1 protein)compared to that in WKY rats (k = 0.085 day-1; tl/2= 8.1 days; r/k = 54 fmol mg-1 protein) and that the reduced density of cortical alpha2-adrenoceptors (Bmax or r/k values) in SHR was probably due to an abnormal higher receptor degradation (delta k = 66%) and not to a decreased receptor synthesis which in fact showed a slight increase (delta r = 24%).6. Treatment with clorgyline (1 mg kg-1, i.p. for 21 days) accelerated the turnover of brain alpha2-adrenoceptors in WKY rats (k = 0.328 days-1; tl/2= 2.1 days; r/k = 29 fmol mg-1 protein) and the greater increase in receptor degradation (delta k = 286%) over receptor synthesis (delta r = 109%) led to down-regulation of receptor density (r/k = 46% lower). In contrast, treatment with clorgyline did not modify significantly the turnover of brain M2-adrenoceptors in SHR (k = 0.192 days-1; t1/2 = 3.6 days;r/k = 39 fmol mg-1 protein), indicating that in this genetic model of hypertension, the desensitized alpha2-adrenoceptors cannot be further down-regulated by clorgyline treatment and that they lack the expected adaptative increase in receptor synthesis.

Adrenergic alpha-Agonists↗
PubMed1983

[Effect of protein denaturing reactions on retardation of the activity of rat liver mitochondrial monoamine oxidase by clorgyline and deprenyl].

The denaturating effects of urea on clorgyline-produced inhibition of serotonin and tyramine deamination and deprenyl-produced inhibition of beta-phenylethylamine and tyramine oxidation were studied. It was shown that after preincubation of mitochondria with 1 and 2 M urea the intensity of inhibition by clorgyline and deprenyl of oxidation of these amines was not changed. With urea concentration of 3 and 4 M the inhibitory effect of clorgyline on deamination of serotonin and tyramine was increased, while that of deprenyl on oxidation of beta-phenylethylamine and tyramine was decreased. As a result of mitochondria treatment with 3 and 4 M urea the selectivity in inhibition by clorgyline of serotonin and tyramine deamination typical for intact mitochondria was reduced in the case of 3 M urea and eliminated in the case of 4 M urea. In intact mitochondria the intensity of inhibition by clorgyline of tyramine deamination in the presence of benzyl alcohol (competitive reversible MAO inhibitor) was increased, but the additive effect was not achieved. However, after preincubation of mitochondria with 3 M urea the summation of the inhibitory effects of clorgyline and benzyl alcohol was observed. The data obtained provide further evidence for the important role of spatial configuration of the monoamine oxidase molecule; the data are discussed in terms of arrangement on the protein molecule surface of the essential groups involved in the binding and deamination of amines for the inhibitory effects of clorgyline and deprenyl.

Animals↗
PubMed1981

[Effect of solubilization by methylethylketone of rat liver mitochondrial monoamine oxidase on inhibition by clorgyline and deprenyl of the enzyme activity].

A comparative study of the inhibitory effect of clorgyline and deprenyl on serotonin, beta-phenylethylamine and tyramine deamination by intact mitochondria as well as by solubilized with methylethylketone and partially purified monoamine oxidase (MAO) from rat liver was carried out. The effect of 4-ethylpyridine on this process was investigated. After solubilization of MAO by methylethylketone 7% of mitochondrial activity passes into solution and the rate of deamination of serotonin, tyramine and beta-phenylethylamine by soluble MAO preparation is selectively decreased. The corresponding residual activities are equal to 29, 63, 86 and 92%. The inhibitory effect of clorgyline on serotonin deamination by soluble MAO preparations is considerably lower than that by mitochondrial suspensions at the concentrations of the inhibitor from 1 x 10(-4) to 1 x 10(-7) M, while the inhibitory action of clorgyline on tyramine deamination after MAO solubilization by methylethylketone is increased at 10(-4) and 10(-5) M, but decreased insignificantly at 10(-6) and 10(-7) M. When solubilized MAO preparations are used, 4-ethylpyridine introduced into the sample before or after preincubation of the enzyme with clorgyline (30 min, 23 degrees) eliminates the inhibitory action of the latter on serotonin and tyramine deamination, thus suggesting the reversibility of the inhibitory effect of clorgyline. In similar experiments with mitochondrial suspensions the inhibition by clorgyline of deamination of these amines is irreversible. Similar experiments on mitochondrial suspensions showed that clorgyline irreversibly inhibits the deamination of these amines. The rate of inhibition by deprenyl of beta-phenylethylamine oxidation due to MAO solubilization by methylethylketone is not changed. 4-Ethylpyridine added to the samples before or after preincubation of deprenyl with the enzyme (30 min, 23 degrees) abolishes the inhibiting effect of the former both in soluble MOA and in mitochondrial suspensions. This suggests that under the given experimental conditions the inhibiting effect of deprenyl is reversible. Possible nature of MAO forms A and B is discussed.

Animals↗