Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SALICYLAMIDE”

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 757 records · Page 42Linked to original sources
PubMed1988

Human dopamine receptor subtypes--in vitro binding analysis using 3H-SCH 23390 and 3H-raclopride.

Affinities and regional densities of the D1- and D2-dopamine receptor subtypes were studied in the human post-mortem brain in vitro using the two selective radioligands 3H-SCH 23390 and 3H-raclopride. 3H-Raclopride binding was confined to the caudate nucleus, the putamen and the substantia nigra, while 3H-SCH 23390 bound to cortical regions as well. The binding of 3H-SCH 23390 was reduced by a low concentration of ketanserin, indicating binding to 5-HT2 receptors in addition to the D1-dopamine receptors. The endogenous neurotransmitter dopamine interacted potently both with the D1-dopamine receptor and the D2-dopamine receptor, displaying two affinity states for each subtype. The distribution of the dopamine receptor subtypes obtained in the present in vitro investigation is in agreement with data obtained with 11C-SCH 23390 and 11C-raclopride in positron emission tomographic studies in human volunteers.

Adult↗
PubMed1991

Difference in in vivo receptor binding between [3H]N-methylspiperone and [3H]raclopride in reserpine-treated mouse brain.

The in vivo binding of [3H]N-methylspiperone (NMSP) and [3H]raclopride was compared in mice treated with reserpine (5 mg/kg, 24 hr prior to the tracer injection). With both radioligands, selective accumulation of radioactivity in the striatum following intravenous injection was observed, whereas a relatively low accumulation and a rapid decline in radioactivity in the cerebellum was seen. Reserpine significantly decreased [3H]NMSP binding in vivo, however it increased [3H]raclopride binding. By compartment model analysis, it was found that the decrease in [3H]NMSP binding was primarily due to the decrease in the association rate (K3) and the increase in [3H]raclopride was due to the decrease in the dissociation rate (K4) in vivo. As both Kd and Bmax of dopamine D2 receptors have been reported to be unaltered by reserpine, these results suggested that some unknown factors except Kd and Bmax which influence on in vivo binding of receptors might be changed by reserpine. These results revealed that it is of importance to measure kinetics of ligand-receptor binding in vivo rather than static analysis. These two different types of radioligands can be combined to reveal functional roles of dopamine receptor in vivo, especially in the study of the human brain with positron emission tomography (PET).

Animals↗
PubMed1993

The dopamine D3-receptor: a postsynaptic receptor inhibitory on rat locomotor activity.

We report on the pharmacological effects of the 20 fold D3 vs. D2 dopamine receptor preferring compound U99194A. It is shown that U99194A increases rat locomotor activity at doses that do not increase release or utilisation of dopamine in the striatum or the nucleus accumbens significantly. The data do not support any direct agonist action of U99194A at dopamine receptors. It is suggested that U99194A can antagonise a population of postsynaptic dopamine receptors involved in the suppression of some aspects of psychomotor activity. These postsynaptic receptors presumably belong to the D3 receptor subtype.

Aminoquinolines↗
PubMed1989

In vivo labelling of pituitary dopamine D-2 receptors in the male rat using [3H]-raclopride.

The substituted benzamide drug [3H]-raclopride (Köhler et al., 1985) was used to label dopamine D-2 receptors within the individual lobes of the pituitary gland as well as in the brain of male rats in vivo. The in vivo [3H]-raclopride binding was found to be saturable, reversible and of high specificity. Between 5-30% of the binding was non-specific at saturating concentrations dependent upon the lobe of the pituitary gland as well as of the brain region (e.g., caudate nucleus and olfactory tubercle) studied. Saturation analyses revealed Bmax-values of 12.9 +/- 1.6 and 2.2 +/- 0.9 pmol.g-1 wet weight in the intermediate and anterior lobes, respectively with respective KD values of 6.5 +/- 4.6 and 7.3 +/- 2.4 nmol.kg-1. Quantitative autoradiographic studies using a single concentration of [3H]-raclopride showed a similar relationship with regard to binding densities in the different lobes, and showed, in addition, that the posterior lobe contained the lowest number of specific [3H]-raclopride binding sites. The binding capacities and affinities of binding were 12.9 +/- 1.7 and 9.2 +/- 2.8 respectively in the caudate nucleus and 6.1 +/- 0.7 and 9.3 +/- 2.7 respectively in the olfactory tubercle. The pharmacological analysis revealed that (S)sulpiride, remoxipride and raclopride were 10 to 125 times more potent than their corresponding isomers [(R)sulpridie, FLA 731(--), and FLB 472, respectively] in blocking the in vivo [3H]raclopride binding in the pituitary gland as well as in brain. The in vivo potency of different D-2 antagonists in preventing the [3H]-raclopride binding in the anterior and intermediate lobes was: spiperone greater than domperidone greater than raclopride greater than (S)sulpiride greater than remoxipride. The D-1 selective antagonist SCH 23390 did not block the in vivo binding of [3H]-raclopride neither in the pituitary lobes nor in the brain. In agreement with these findings the D-2 agonists N,N-propylnorapomorphine and quinpirole (LY 171555) but not the D-1 agonist SKF 38393-A blocked the specific in vivo [3H]-raclopride binding in the pituitary gland as well as in the brain. Comparisons between the relative potencies of different drugs in blocking pituitary and brain D-2 receptors in vivo showed that some drugs, including sulpiride and domperidone, were more potent in the pituitary gland than in the brain, while remoxipride and raclopride were equipotent in the two areas. The D-2 agonists tested appeared to be slightly more potent in the brain than in the pituitary gland.

Animals↗
PubMed1993

Dopamine D2 blocking activity and plasma concentrations of remoxipride and its main metabolites in the rat.

Remoxipride and its active metabolites, the phenolic compounds FLA797(-) and FLA908(-) and the catecholic NCQ436(-) and haloperidol, were examined for their ability to block hypothermia in the rat induced by dopamine (DA) D2 receptor stimulation. In addition, plasma levels of remoxipride and its active metabolites were measured using HPLC methods. Remoxipride (1 mumol/kg), given 30 or 15 min prior to, or 5 and 15 min after, the DA agonists, blocked the hypothermia induced by the DA D2 receptor agonists quinpirole (0.25 mg/kg s.c.) and pergolide (0.1 mg/kg s.c.). Administration of remoxipride by the i.v. or s.c. routes was more effective than by the i.p. route. FLA797(-), FLA908(-), and haloperidol were more effective than remoxipride in preventing the hypothermia caused by quinpirole, while NCQ436(-) was less effective than remoxipride. The variation in time of remoxipride's action and effectiveness in blocking the induced hypothermia followed the variations in plasma concentrations. The plasma concentrations of the active metabolites were below the limit of determination (< 2 nmol/l). Based on estimation of free brain concentrations at effective dose levels together with in vitro affinities for the DA D2 receptor it was concluded that the metabolites FLA797(-), FLA908(-), and NCQ436(-) do not appear to contribute to the antagonism of DA D2 mediated neurotransmission following a low remoxipride dose (1 mumol/kg).

Animals↗
PubMed1990

Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats.

Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2 ([3H]spiperone and [3H]raclopride), dopamine D 1 ([3H]SCH23390), GABA(A) ([3H]muscimol), benzodiazepine ([3H]RO15-1788), and muscarinic ACh receptors ([3H]QNB). [3H]spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal [3H]raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in [3H]SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in [3H]muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of [3H]QNB and [3H]RO151788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride.

Animals↗
PubMed1993

Dopamine-glutamate interactions in methamphetamine-induced neurotoxicity.

Repeated administration of methamphetamine (m-AMPH) to rats induces dopamine (DA) terminal damage, and coadministration of antagonists of the N-methyl-D-aspartate (NMDA) or dopamine D1 or D2 receptors are protective. Striatal microdialysis of rats given a neurotoxic regimen of 4 x m-AMPH (4 mg/kg, s.c.) treatments revealed a dramatic and prolonged elevation of extracellular DA after the final m-AMPH administration. Neuroprotective regimens of MK-801, SCH 23390, or eticlopride greatly attenuated the overflow of DA resulting from the fourth m-AMPH treatment. By itself, MK-801 had no significant influence on striatal DA overflow, whereas either DA antagonist given alone elevated dialysate DA concentrations. A significant correlation was found between the magnitude of the m-AMPH-induced DA overflow of individual microdialyzed rats and their striatal DA content at sacrifice one week later. We conclude that the ability of non-competitive NMDA antagonists and of the D1 or D2 antagonists to protect against m-AMPH-induced striatal DA terminal injury can be accounted for by their attenuation of m-AMPH-evoked DA overflow. These findings underscore the important role played by elevated extracellular DA concentrations to the injurious effects of this stimulant drug.

Animals↗
PubMed1992

Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats.

The effects of typical and atypical neuroleptics on MK-801-induced locomotor activity and stereotyped sniffing were tested. Pretreatment with the typical neuroleptic haloperidol (0.01, 0.05, 0.1, 0.5 mg/kg SC) and the dopamine D2 receptor selective antagonist eticlopride (0.005, 0.01, 0.05 mg/kg SC) each resulted in significant and dose-dependent reductions of locomotor activity and sniffing. The atypical neuroleptic clozapine (1.0, 5.0, 10.0 mg/kg SC) was somewhat unique in that all doses reduced locomotor activity, but only the highest dose (10.0 mg/kg) significantly reduced sniffing. The data support a functional interaction between glutamate and dopamine systems, and suggest that the behavioral activation associated with MK-801 may represent a valid model for detecting potential therapeutic agents in the treatment of schizophrenia. The data should be viewed as preliminary, however, until neuroleptics are characterized in other glutamate-based models that minimized or exclude the possible influence of nonspecific motor effects.

Animals↗
PubMed1992

Antagonism by 8-OH-DPAT, but not ritanserin, of catalepsy induced by SCH 23390 in the rat.

In the present experiments, it was shown that the catalepsy induced by the dopamine D1 antagonist SCH 23390 (0.2 mg kg-1 sc), was completely antagonised by the administration of 8-OH-DPAT (0.1 mg kg-1 sc) for the duration of the effect of SCH 23390 (approx. 120 min). Neither the catalepsy induced by raclopride (16 mg kg-1 sc) nor that induced by SCH 23390 (0.2 mg kg-1 sc) could be antagonised by treatment with the 5-HT2 receptor antagonist ritanserin (0.13-2.0 mg kg-1 sc). Administration of SCH 23390 (0.0125-0.2 mg kg-1 sc) produced a significant suppression of avoidance behavior at all doses, and also produced a significant decrease in the number of intertrial crosses. At the higher doses, 0.05 and 0.2 mg kg-1 sc, there were also escape failures. In contrast to the finding in our previous report that raclopride and 8-OH-DPAT in a synergistic manner produce a suppression of conditioned avoidance behavior, no such interaction was found between 8-OH-DPAT (0.1 mg kg-1 sc) and SCH 23390 (6 micrograms kg-1 sc) in the present study.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Differential locomotor interactions between dopamine D1/D2 receptor agonists and the NMDA antagonist dizocilpine in monoamine-depleted mice.

Previous work in our laboratory has shown that the non-competitive N-methyl-D-aspartate antagonist dizocilipine (MK-801) interacts synergistically with the mixed dopamine (DA) receptor agonist apomorphine and the DA D 1 agonist SKF 38393 to promote locomotion in monoamine-depleted mice. The purpose of the present study was to compare the roles of DA D 1 and DA D 2 receptors in this interaction. To that end, dizocilpine was given in combination with either the DA D 1 receptor agonist SKF 38393 or the selective DA D 2 receptor agonist quinpirole or the preferential DA D 2 agonist bromocriptine. In general, the locomotor stimulatory effects produced by SKF 38393 were potentiated by dizocilpine, whereas the locomotor stimulation produced by quinpirole and bromocriptine was counteracted. However, baseline activity, which partly depends on how much time is allowed to elapse between administration of the DA agonist and commencement of locomotor recording, and partly on the dose of the DA agonist, seems to be an important factor that determines whether dizocilpine will have a weakening or a potentiating effect. Interestingly, the competitive NMDA antagonist D-CPPene displayed a different pattern of interaction with SKF 38393 and quinpirole in that synergistic effects were observed with both DA agonists, most conspicuously so with the DA D 2 receptor agonist. The results are interpreted in the light of present knowledge of basal ganglia neuroanatomy; they are discussed in relation to the "direct" and "indirect" pathways from the striatum to the thalamus, proposed to form part of positive and negative cortico-striato-thalamo-cortical loops, respectively, as well as to the presumed presynaptic D 2 receptors on corticostriatal glutamatergic neurons.

Animals↗
PubMed1992

Regional distribution and in vivo binding of the atypical antipsychotic drug remoxipride. A biochemical and autoradiographic analysis in the rat brain.

The regional brain distribution and binding of the antipsychotic benzamide drug remoxipride was studied in the male rat. After i.v. injections of 3H-remoxipride (1 mumol.kg-1) more than 85% of the radioactivity was identified as authentic remoxipride in brain by using reversed-phase liquid chromatography. Autoradiographic and spectroscopic analysis showed that 3H-remoxipride was distributed relatively even in different brain areas, with exception of the following structures, which showed highest drug concentrations: the choroid plexus, septum, medial part of the caudate nucleus, different areas of the thalamus and hypothalamus situated close to the cerebral ventricles. A closer analysis of the autoradiograms showed a gradient of radioactivity extending from the cerebral ventricles to the deeper parts of the brain at 30 minutes after injections. After 60 minutes radioactivity was detected throughout all forebrain dopamine receptive areas. These findings suggest that remoxipride enters the cerebrospinal fluid (CSF) via the vascular bed of the choroid plexus and that it enters the brain interstitial fluid from the CSF. In the caudate nucleus, nucleus accumbens, olfactory tubercle and olfactory bulb 30-40% of the radioactivity was reduced by pretreatment with the dopamine D-2 selective drug raclopride. In addition, small, but significant, reductions (10-15%) of 3H-remoxipride derived radioactivity was found in the neocortex, hippocampus and the cerebellum, suggesting that remoxipride interacts with a D-2 receptor also in these cortical structures. Taken together, these studies show that after i.v. injections, 3H-remoxipride enters the brain primarily in unmetabolized form when given in doses that affect DA receptor mediated behaviours, that it distributes to most areas throughout the neuraxis and that it binds to D-2 receptors in different parts of the basal ganglia, neocortex, hippocampus and cerebellum.

Animals↗
PubMed1996

Antipsychotics with inverse agonist activity at the dopamine D3 receptor.

In NG 108-15 cells expressing the recombinant human D3 receptor, dopamine agonists enhance [3H]thymidine incorporation and decrease cAMP accumulation. In these cells, but not in wild type cells, haloperidol, fluphenazine, and various other antipsychotics inhibited basal [3H]thymidine incorporation in a concentration-dependent manner. In contrast, other dopamine antagonists such as nafadotride or (+)AJ 76, two D3-preferring antagonists, were without effect. The concentration-response curve of haloperidol was shifted to the right in presence of nafadotride, with a potency compatible with its nanomolar apparent affinity as neutral antagonist. Pertussis toxin treatment abolished or markedly reduced the responses to haloperidol or fluphenazine. In contrast, no significant enhancement of cAMP accumulation could be observed, under the influence of haloperidol or eticlopride. These data indicate that some dopamine antagonists behave as inverse agonists, and thus appear to inhibit an agonist-independent activity of the D3 receptor on [3H]thymidine incorporation pathway, but not on the cAMP pathway.

Animals↗
PubMed1996

Monoamine oxidase gene transcription in human cell lines: treatment with psychoactive drugs and ethanol.

In the present study transcriptional activities has been measured with different fragments of the 5'-flanking sequence of the human monoamine oxidase (MAO) genes linked to human growth hormone which was used as a reporter gene. SH-SY5Y neuroblastoma cells and 1242 MG glioma cells were compared under basal conditions as well as after treatments with different drugs. Under basal conditions, the relative reporter activities of the different promoter fragments were similar for both cell lines. No changes in promoter activities, were observed when cells were treated with L-deprenyl, lithium chloride or raclopride. In contrast, increases (2-3-fold) in both reporter gene expression and enzyme activity were observed after ethanol treatment of cells transfected with MAO-B fragments. Gel retardation analysis showed that ethanol caused changes in transcription factor binding to the MAO-B core promoter in both the SH-SY5Y and 1242 MG cell lines in a cell-type specific fashion.

Alcohol Drinking↗
PubMed1996

Effects on locomotor activity after local application of (+)-UH232 in discrete areas of the rat brain.

The preferential dopamine autoreceptor, and slightly D3 preferring, antagonist (+)-UH232 (cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-dipropylamino) tetralin) increases locomotor activity and synaptic dopamine release in the nucleus accumbens and striatum after systemic administration to the rat. As shown in this study, (+)-UH232, was unable to produce an increase in locomotor activity measured for 60 minutes after local administration into the terminal or somato-dendritic regions of the mesolimbic dopamine pathways or into the lateral ventricle. Instead, a dose dependent decrease of spontaneous locomotor activity after local application (0.05-50.0 nmol/side) of (+)-UH232 into the nucleus accumbens, was seen. A similar reduction in locomotor activity was produced by the classical dopamine antagonist raclopride. Analysis of the dose*time interactions on locomotor activity did, however, indicate that there is a significant dose*time interaction after local application of (+)-UH232 into the lateral ventricle and VTA. Raclopride, on the other hand, produced only a weak time dependent effect in the VTA. The potential problem of Leao's spreading depression in micro-injection experiments were considered, however, spreading depression does not seem to influence the effects of (+)-UH232 locally applied into the nucleus accumbens. In conclusion, both (+)-UH232 and raclopride produced a dose dependent decrease in spontaneous locomotor activity when examined as the total activity count over 60 minutes after local application into the N Acc.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Pharmacological modifications in dopaminergic neurotransmission affect the quinpirole-evoked suppression of serotonin N-acetyltransferase activity in chick retina: an impact on dopamine D4-like receptors.

Dopamine (DA) plays an important role in the regulation of melatonin biosynthesis in retinas of several vertebrate species. In the retina of chick, the DA receptor controlling melatonin production represents a D4-like subtype. Stimulation of this receptor by quinpirole (QNP) results in a dose-dependent decline of the nighttime activity of serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthesis) and melatonin level of chick retina. The present study was undertaken to determine whether long-term treatment with antipsychotic drugs (clozapine-30 mg/kg, i.m.; sulpiride-100 mg/kg, i.m.; and raclopride-10 mg/kg, i.p., once daily for 21 days) and L-DOPA (80 mg/kg, i.p., once daily for 7 days) affects the response of the melatonin generating system of chick retina to the suppressive effect of QNP. Chronic administration to chicks of clozapine and sulpiride, but not raclopride, resulted in a markedly increased response of retinal NAT activity to the action of QNP. ED50 values for QNP were 3-times (clozapine) and 4-times (sulpiride) lower than those in the respective vehicle-treated control groups. On the other hand, QNP was significantly less potent in retinas of birds treated with L-DOPA than in control animals; the ED50 value for QNP was 3-times higher in birds injected with L-DOPA than in the vehicle-treated group. These results indicate that long-term treatment with clozapine, sulpiride and L-DOPA may modify the reactivity of D4-like DA receptors regulating NAT activity of chick retina. A possibility of modifications of circadian and electrophysiological processes within the eye following prolonged administration of DA-ergic drugs is discussed.

Animals↗
PubMed1995

Difference in response of D2 receptor binding between 11C-N-methylspiperone and 11C-raclopride against anesthetics in rhesus monkey brain.

The effects of anesthesia on dopamine D2 receptor binding in the rhesus monkey brain were examined using positron emission tomography. The bindings of 11C-N-methylspiperone (NMSP) and 11C-raclopride (RAC) were measured under controlled ketamine or isoflurane anesthesia. The binding of 11C-NMSP was significantly lower in the striatum anesthetized with isoflurane than with ketamine. There was a smaller change in the binding of 11C-RAC than of 11C-NMSP. These findings suggest that changes in 11C-NMSP or 11C-RAC binding induced by anesthetics were not due solely to changes in the competition of endogenous dopamine.

Anesthetics↗
PubMed1994

On the roles of dopamine D-1 vs. D-2 receptors for the hyperactivity response elicited by MK-801.

The present study was aimed at clarifying to what extent the hypermotility induced by the uncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 depends on dopamine (DA) D-1 compared to D-2 receptor tone. The D-1 receptor antagonist SCH 23390 was found to reduce locomotion to a greater extent in MK-801-treated than in vehicle-treated mice, whereas the reverse appeared to be the case for the DA D-2 receptor antagonist raclopride. In other words, MK-801-induced hyperactivity was more readily antagonized by SCH 23390 than by raclopride and, thus, DA D-1 receptors seem to be more important than D-2 receptors for MK-801-induced hyperactivity. These results are in line with our previous observation that MK-801 generally interacts synergistically with a DA D-1 but not with a D-2 receptor agonist in monoamine-depleted mice. In view of the possible role of deficient glutamatergic neurotransmission in schizophrenia, our findings underline the importance of investigating the efficacy of selective DA D-1 antagonists in this disorder.

Animals↗
PubMed1993

Concentrations of remoxipride and its phenolic metabolites in rat brain and plasma. Relationship to extrapyramidal side effects and atypical antipsychotic profile.

The cataleptic effect of remoxipride was examined in the horizontal bar test after i.v.,i.p. and s.c. administration to male rats. Remoxipride induced immediate catalepsy after high i.v. doses (ED50 = 49 mumol/kg) while peak effects were seen 60-90 min after i.p. administration (ED50 = 38 mumol/kg). Following s.c. administration remoxipride failed to produce a statistically significant catalepsy in the 20-100 mumol/kg dose range (ED50 > 100 mumol/kg). In contrast, haloperidol was found to be more effective in inducing catalepsy after i.v. (ED50 = 0.4 mumol/kg) than after i.p. or s.c. administration (ED50 = 0.9 mumol/kg). The atypical antipsychotic profile of remoxipride was more pronounced when the compound was given i.v. or s.c. as compared with the i.p. route. Plasma and brain (striatum and nucleus accumbens) concentrations of remoxipride and its active phenolic metabolites FLA 797(-) and FLA 908(-) were measured by high performance liquid chromatography. The 40 mumol/kg dose of remoxipride resulted in plasma and brain concentrations of remoxipride which were 300-1000-fold higher (depending on the route of administration) than the most potent of the phenolic metabolites, e.g., FLA 797(-). The plasma and brain concentrations of remoxipride and its phenolic metabolites were related to DA D2 receptor blocking potency and to the temporal course and effectiveness to induce catalepsy. This analysis suggested that the unbound concentrations of the phenolic metabolites were too low to play a major role in the DA blocking action of remoxipride. However, FLA 797(-) may contribute marginally to the cataleptic effects following high (i.p.) doses of remoxipride.

Animals↗