Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Butaclamol”

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 325 records · Page 18Linked to original sources
PubMed1982

Is alcohol induced poikilothermia mediated by 5-HT and catecholamine receptors or by ionic set-point mechanism in the brain?

In adult male Sprague-Dawley rats, stainless steel guide cannulae were implanted stereotaxically in either the lateral or third cerebral ventricle. Postoperatively, each animal was maintained at an ambient temperature of 22 degrees C. Just prior to the intragastric gavage of 4.0 g/kg ethyl alcohol (20% solution) individual animals were fitted with a colonic thermistor probe. Then, control CSF, a monoaminergic receptor antagonist, or a Ca++ ion chelating agent, EGTA, was infused into either the lateral or third ventricle (ICV) in a volume of 10.0 microliter. Phentolamine (20.0 micrograms), butaclamol (10.0 micrograms), or methysergide (20.0 micrograms) injected ICV all failed to prevent the thermolytic action of alcohol. The fall of 1.5 to 2.0 degrees C in the rat's colonic temperature, ordinarily caused by alcohol, was the same as that without the antagonists and lasted 3.0 to 4.0 hrs. EGTA infused into the rat's lateral cerebral ventricle also did not interfere with alcohol's poikilothermic action. However, EGTA infused into the third cerebral ventricle completely blocked alcohol's effect in lowering the body temperature of the rat. These results suggest that: (1) alcohol's profound effects on body temperature are not mediated by 5-HT, norepinephrine or dopamine pathways which are thought to underlie the mechanisms in the hypothalamus for thermoregulation; and (2) the temperature set-point mechanism, controlled by the ratio of diencephalic Na+ to Ca++ ions, is incapacitated by alcohol. Restoration of the ratio in the diencephalon by the direct, local chelation of Ca++ ions that eliminates alcohol's deleterious effects on body temperature.

Animals↗
PubMed1993

Discriminative stimulus effects of the PCP/sigma-ligand (+)-N-allylnormetazocine in monkeys.

(+)-N-Allylnormetazocine [(+)-NANM] binds to both the phencyclidine (PCP) receptor and the sigma-site in brain, with some selectivity for the latter. In rats, the discriminative stimulus effects of (+)-NANM are primarily PCP like. The present study was performed to determine if the discriminative effects of (+)-NANM in a primate species might reflect the actions of this drug at the sigma-site. Six squirrel monkeys were trained to discriminate between IM injections of saline and 1.0 mg/kg (+)-NANM in a two-choice discrete-trial avoidance procedure. In tests of stimulus generalization, dose-dependent increases in trials completed on the (+)-NANM choice lever were produced by (+)- and (-)-NANM, by PCP and the PCP-like drugs MK-801 and thienylcyclohexyl-piperidine, and by the opioids (+)- and (-)-cyclazocine and dextrorphan; order of potency correlated with reported affinities for the PCP receptor. High-affinity sigma-ligands, (+)-pentazocine, 1,3-di-ortho-tolylguanidine (DTG), haloperidol, and BMY 14802, as well as agonists at mu- and kappa-opioid receptors, occasioned selection of the saline-appropriate choice lever. Selection of the (+)-NANM choice lever was reduced by up to 35-50% when 1.0 mg/kg (+)-NANM was given concurrently with haloperidol or BMY 14802, but was not affected substantially by (-)-butaclamol, another sigma-ligand, or by naltrexone, an opioid antagonist. The discriminative effects of (+)-NANM in squirrel monkeys appear to be mediated largely by the PCP receptor and not by the sigma-site or opioid receptors.

Animals↗
PubMed1985

Ontogeny of dopamine, serotonin and spirodecanone receptors in rat forebrain--an autoradiographic study.

Sections from freshly frozen neonatal rat brain, ages 0-21 days, were incubated with [3H]spiperone (SP). Initial studies characterized the binding sites for SP in terms of association and dissociation rates, saturability and pharmacology. The binding sites were found to be predominantly dopamine D2 receptors in sections centered in the striatum and these receptors were similar to receptors in adult brain. Autoradiographic studies using in vitro techniques examined the anatomic distribution of [3H]SP binding sites. Using domperidone, ketanserin and (+)butaclamol it was possible to differentiate dopamine D2, serotonin S2 and spirodecanone receptors. Dopamine receptors were found at birth in striatum and nucleus accumbens and increased in density with age. In the first two weeks postnatally there was an apparent dorsolateral to ventromedial gradient in the striatum. Serotonin S2 receptors were found in the cortex, lateral olfactory tubercles and nucleus accumbens and claustrum. These receptors increased in density with age but to a much lesser extent than dopamine receptors. Spirodecanone receptors were first apparent in the piriform cortex by day 5. They became very dense with age in particular regions, i.e., layer II of cortex, piriform cortex, medial olfactory tubercles, lateral septum and in patches in the nucleus accumbens. These studies delineate with a high resolution at an anatomical level the major receptor sites for neuroleptic drugs in the developing rat forebrain. They describe the developmental pattern of these receptors and provide a basis for further studies on their control and function during development.

Animals↗
PubMed1989

High affinity dopamine binding to mouse thymocytes and Mytilus edulis (Bivalvia) hemocytes.

The present report demonstrates that both mouse thymocytes and Mytilus edulis hemocytes contain a novel type of dopamine receptor. Scatchard analysis of these data revealed a single class of high-affinity binding sites with an affinity constant (Kd) of 6.6 nM, and a binding site density (Bmax) of 141 pmol/g protein in mice and a Kd of 7.6 nM and a Bmax of 66 pmol/g protein for the hemocytes. In older Mytilus the Kd was the same; however, there was a significant decrease in the Bmax (48 pmol/g protein; P greater than 0.05). Age changes were not evident for the mouse cells. The ability of a variety of other related drugs to displace specifically bound dopamine was investigated. The catecholamines (norepinephrine greater than epinephrine) and the dopamine agonist epinine were the most potent of the ligands tested and apomorphine and butaclamol were of moderate potency. This may serve to indicate that this dopamine binding site may be very different from the known D1 and D2 sites. This particular site may represent a third type of dopaminergic receptor. Furthermore, the hemocytes of Mytilus appear to be of two major types, namely, cells with a granular cytoplasm and those whose cytoplasm is agranular. Histofluorescence studies on the hemocytes reveal that a subpopulation of the granule-containing cells appears to contain serotonin.

Animals↗
PubMed1992

A study of the kinetics of the interaction of spiperone with binding sites on human mononuclear cells: existence of a heterogeneous population of spiperone binding sites.

The kinetics and equilibrium of the interaction of [3H]spiperone with binding sites on human mononuclear cells were studied using a competitive displacement of spiperone by ketanserin, sulpiride, haloperidol, (+)- and (-)-butaclamol. [3H]Spiperone binding sites on human mononuclear cells were shown to be not of the D2, but most probably of the 5-HT2 type. The process of [3H]spiperone binding to these sites conforms to the model of ligand interaction with two independent binding sites (the high-affinity site, Kd1 = 3 nM and the low-affinity site, Kd2 = 20 nM), thus suggesting heterogeneity of spiperone sites on mononuclear cells. We found that in contrast to high-affinity binding sites, low-affinity sites show an essentially lower stability during storage of mononuclear cells.

Binding Sites↗
PubMed1994

Dopamine receptor regulating serotonin N-acetyltransferase activity in chick retina represents a D4-like subtype: pharmacological characterization.

The dopamine (DA) receptor regulating serotonin N-acetyltransferase (NAT) activity in chick retina was characterized pharmacologically. Intraocular (i.o.) administration of DA significantly decreased the nighttime NAT activity of chick retina. The effect of DA was antagonized by blockers of the D2 family of DA receptors, spiroperidol, YM-09151-2 and clozapine, and it was not affected by SCH23390, a selective antagonist of D1 DA receptor. Several agonists of D2 family of DA receptors given i.o. suppressed the nighttime NAT activity of the chick retina with quinpirole (D3/D4 receptor selective) and bromocriptine (D2/D3 receptor selective) being the most and the least potent drugs, respectively. The rank-order potency of antagonists of D2 family of DA receptors to block the inhibitory effect of quinpirole on the enzyme activity (with clozapine being relatively very potent, and (+)-butaclamol, raclopride and remoxipride-ineffective) match the characteristics of the D4 DA receptor. Moreover, although sulpiride effectively prevented the quinpirole-induced decline in the nighttime NAT activity of the chick retina, there was no marked stereoselectivity in its action. It is suggested that DA receptor regulating NAT activity in chick retina represents a D4-like subtype.

Animals↗
PubMed1984

Rat anterior pituitary cells maintained on artificial capillaries: responses of thyrotrophs and lactotrophs to depolarization, TRH and dopamine.

Rat anterior pituitary cells have been maintained over an 18-day period in a perfusion system designed around artificial capillaries. Using novel methodology the cells have been visualized by light microscopy and appear as aggregates, closely attached to and sometimes stretching around the capillaries. Their morphology is consistent with previous histology at the level of light microscopy. The techniques described are compatible with immunohistochemistry and electron microscopy. The functional integrity of thyrotrophs and lactotrophs maintained in the system has been examined by measuring the dynamics of TSH and PRL secretion in response to depolarization, TRH and dopamine (DA). TSH and PRL were significantly and reproducibly released by TRH over a 7-day period. On each day the release was dose-dependent with a threshold of at least 28 pg. Qualitatively the responses were rapid in onset (within minutes) for both hormones. Similar responses were measured in response to high K+ depolarization. Basal secretion of TSH and PRL was rapidly and significantly inhibited by DA in a dose-dependent manner (ED50 20 +/- 25 nM for TSH and 70 +/- 40 nM for PRL). Inhibition was dependent on the continued presence of DA and could be mimicked by bromocriptine and stereospecifically prevented by the active but not the inactive isomer of the DA receptor antagonist butaclamol. Simultaneous administration of 10(-6) M DA with 10(-8) M TRH prevented the release of TSH and PRL. The effect of DA was transient, subsequent TRH responses being qualitatively and quantitatively normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Evidence for the existence of a dopamine receptor of the D-1 type in the rat median eminence.

By means of receptor autoradiography using the dopamine (DA) receptor radioligands [3H]cis(z)-flupenthixol ([3H]FLU), [3H]spiperone, [3H]N-propyl-norapomorphine and amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphtalene-2-(5,8[3H]) in combination with a microdensitometrical analysis indications have been obtained for the existence of a DA receptor of the D-1 type in the median eminence of the male rat. Thus, only [3H]FLU (10-20 nM) strongly labeled both the nuc. caudatus putamen and the median eminence and the labeling was markedly prevented by (+)-butaclamol in both regions. Furthermore, a DA receptor agonist of the D-1 type preferentially displaced [3H]FLU from the median eminence. Thus, a DA receptor of the low affinity type may regulate the secretion of hypothalamic hormones from the median eminence.

Animals↗
PubMed1986

Autoradiographic visualization of dopamine D-2 receptors in the monkey brain using the selective benzamide drug [3H]raclopride.

Using the novel substituted benzamide drug [3H]raclopride in combination with in vitro receptor autoradiography, the distribution of dopamine D-2 receptors was studied in the monkey brain. Highest densities of D-2 receptors are present in dopamine-rich areas and the distribution shows the following rank order: caudatus and putamen greater than nucleus accumbens greater than olfactory tubercle greater than substantia nigra (pars compacta) greater than insular cortex greater than piriform and entorhinal cortex greater than substantia nigra (pars reticulata). In all of these areas [3H]raclopride binding was blocked by dopamine (1 microM) and by D-2 receptor antagonists such as (+)-butaclamol, eticlopride and raclopride, while the D-1 receptor antagonist SCH 23390 (1 microM) reduced [3H]raclopride binding by 15-20% in some restricted parts of the caudatus and putamen exclusively.

Animals↗
PubMed1989

Behavioral and neurochemical modifications induced by apomorphine treatment.

By means of quantitative receptor autoradiography, the modifications of dopamine (DA) receptors in selected target regions of A9 and A10 DA neurons were studied after chronic apomorphine treatment, at a dosage able to induce behavioral changes that are claimed to be due to the activation of the target areas of A9 neurons. An increase in [3H]spiperone binding sites (cold (+)-butaclamol) was observed in the dorsal and ventrolateral striatum, receiving fibers from A9 neurons, while there were no changes in the ventromedial and ventrocentral striatum, in the nucleus accumbens and in the cerebral cortex receiving fibers from A10 neurons. Our results suggest that the anatomical division of the DA target regions corresponds with a functional one.

Animals↗
PubMed1995

Effects of YM 435 and A 77636 on dopamine D-1 receptors in bovine retina in vitro.

1. Homogenates of bovine retinas were used to study the capacities of two new dopamine (DA) receptor agonists, e.g. YM 435 and A 77636, to interact with D1 receptors. 2. Adenylate cyclase experiments. YM 435 and A 77636 enhanced cAMP accumulation, with EC50 values of 1.97 microM and 22.9 nM, respectively. The receptor-mediated nature of the effects of these two novel D1 agonists was shown by the abilities of both SCH 23390 or (+)-butaclamol to inhibit the agonist-induced increase of cAMP formation. 3. Binding experiments. The same agonists were also tested for competition with 3H-SCH 23390 for binding to D1 receptors. IC50 values for YM 435 and A 77636 were 8.15 microM and 6.15 nM, respectively. 4. The results of the present report demonstrate the suitability of bovine retina in vitro to evaluate the specificity of new DA D1 agonists at the receptor level.

Adamantane↗
PubMed1986

Taurine interferes with spiperone binding in the striatum.

The effects of taurine and its structural analogues and two new anticonvulsant derivatives, taltrimide and MY-103, on the function of brain dopaminergic systems were studied by assessing their interference with the binding of [3H]spiperone to synaptic membranes isolated from rat striata. Two populations of binding sites were detected. The binding was effectively displaced by (+)butaclamol and dopamine, serotonin being less potent by one order of magnitude. Taurine, taltrimide and MY-103 inhibited spiperone binding moderately. The binding constants of both high- and low-affinity components and the maximal binding capacity of the low-affinity component decreased in the presence of taurine. The results show that taurine and its novel anticonvulsant derivates could modulate the function of striatal dopaminergic systems.

Animals↗
PubMed1991

Autoradiographic localization of dopamine D1 and D2 receptors in rat nucleus accumbens: resistance to differential rearing conditions.

The radioligands [3H]SCH 23390 and [3H]spiroperidol were used to label dopamine D1 and D2 receptors, respectively, in rat brain slices. Striatal sections were incubated in one of various concentrations of radioligand in the presence or absence of (+)-butaclamol and the resulting labeling was determined by liquid scintillation spectrometry. Scatchard analyses of the data revealed KD values of 1.18 nM for D1 receptors and 0.33 nM for D2 receptors. Tissue sections taken from the entire rostrocaudal extent of the nucleus accumbens, as well as other brain regions, were then processed for autoradiographic analysis of D1 and D2 receptors using a radioligand concentration equal to 1.5 X KD. After apposing the slices to 3H-sensitive film, topographical differences among brain areas were analysed using a quantitative densitometry system which determined the absolute amount of ligand binding relative to calibrated optical density standards. The nucleus accumbens exhibited a rostral-to-caudal density gradient for both D1 and D2 receptors. For D1 receptors, the density was similar across most of the nucleus accumbens, although the most caudal portion examined had a lower density than rostral portions. In contrast, the density of D2 receptors exhibited a more gradual gradient across the entire rostrocaudal extent of the nucleus accumbens. There was no significant rostrocaudal density gradient of either D1 or D2 receptors in either the olfactory tubercle or caudate-putamen in the same tissue sections. A lateral-to-medial gradient of D2 receptors was also present in the nucleus accumbens. That is, while there was no difference in the density of D1 receptors between the lateral core and medial shell subdivisions, the shell had a lower density of D2 receptors than did the core. The density of D1 and D2 receptors in the mesolimbic and nigrostriatal systems was compared in groups of animals raised from 30 to 60 days of age in an impoverished condition, a group-caged condition or an enriched condition. While the brain weight of enriched condition animals was higher than impoverished condition animals, there were no significant differences in the density of D1 or D2 receptors among the different groups. Apparently, the densities of D1 and D2 receptors in the brain are resistant to differential rearing conditions.

Animals↗
PubMedDate not supplied

Effect of lead exposure on dopaminergic D2 receptor binding in the 21-day-old rat.

The effect of lead on dopaminergic D2 receptor binding, as measured by butaclamol-displaceable [3H]domperidone binding, was studied in the 21-day-old lead-dosed rat. Maternal rats were dosed with 300 ppm and 1000 ppm Pb in drinking water from conception to weaning as previously described [1]. Samples of limbic forebrain and striatum were taken from 21-day-old offspring and assayed for dopamine D2-receptor binding, as outlined by Lazareno and Nahorski [2]. There was a significant (P less than 0.05) decrease in body weight in the animals from which limbic forebrain samples were taken. There were no other significant effects of lead on body- or brain weight. Dopaminergic D2 receptor binding was unaffected by lead administration. These preliminary findings show that dopamine D2 receptor binding is not affected by lead at the doses and exposures used.

Animals↗
PubMed1986

Pituitary localization of 3H-spiroperidol by an uptake/storage mechanism?

The lack of a pituitary imaging agent combined with the considerable clinical value for such an agent prompted an examination of 3H-spiroperidol (3HSp). Spiroperidol was selected for initial evaluation based on its high affinity for D2 receptors which are known to be present in the pituitary. A time course study of 3HSp concentration in rat pituitary and other tissues was conducted. Pituitary activity levels were found to be constant from 5 min to 4 h and were about 8 times levels in corpus striatum at 1 h. Blocking studies with (+) butaclamol and with unlabelled spiroperidol suggested the existence of both a D2 receptor mediated binding localization and a second uptake which is postulated to be an internalization process. Further studies involving ultracentrifugation of pituitary homogenates resulted in evidence for association of 3HSp with dense subcellular particles. 3HSp thus appears to be internalized by pituitary cells.

Animals↗
PubMed1986

Use of DES-treated rats as an animal model for assessment of pituitary adenoma imaging agents.

Prolactin (PRL) secreting pituitary adenomas are the most common type of pituitary tumors. An imaging agent which specifically localized in prolactinomas would be of considerable clinical value for both initial detection and also for monitoring the effects of dopamine agonist therapy. Tritiated spiroperidol (3HSp) was selected for initial evaluation as a possible imaging agent based on: demonstrated localization in the pituitary and demonstrated binding to human PRL-secreting tumor tissue. DES was implanted in Fischer F344 rats and induced prolactinoma formation was evidenced by increased pituitary weight, elevated serum PRL levels and by an increase in the proportion of PRL-secreting cells in the pituitary. 3HSp concentrations in pituitary and other tissues of DES-treated rats were assessed in female rats and correlation studies showed that a 5-fold increase in serum PRL was associated with a 6-fold increase in both pituitary weight and % dose/organ accumulation of 3HSp. The number of pituitary D2 receptors per mg of protein in tissue homogenates was similar in both normal and DES-treated females. A blocking study with (+)-butaclamol demonstrated a D2 receptor-mediated component to 3HSp localization. In summary, an animal model for prolactinoma was characterized. An assessment of 3HSp accumulation indicates that radiolabelled spiroperidol shows excellent potential for detecting PRL-secreting tumors of the pituitary.

Adenoma↗
PubMed1992

4-[123I]iodospiperone as a ligand for dopamine DA receptors: in vitro and in vivo experiments in a rat model.

Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Stimulated by data obtained with [11C]-N-methyl-spiperone we synthesized 4-[123I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [3H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[123I]iodospiperone and [3H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich in DA-receptors does not offer prospects for clinical receptor imaging with SPECT.

Animals↗
PubMed1992

Characterization of the binding of [3H](+)-pentazocine to sigma recognition sites in guinea pig brain.

The selective sigma compound (+)-pentazocine was radiolabeled and its binding characteristics in guinea pig brain membranes were investigated. [3H](+)-Pentazocine bound to a single high-affinity site with a KD of 2.9 nM and a Bmax of 1998 fmol/mg protein. Saturation was achieved at a ligand concentration of 15 nM. Maximal specific binding was observed at 37 degrees C and was greater than 90% of total binding. Equilibrium was reached by 120 min and dissociation was complete by 420 min, with a t1/2 of 121 min. Li+, Ca2+ and Mg2+ inhibited binding at high concentrations, and binding was insensitive to adenyl and guanyl nucleotides. Stereoselectivity was observed for the inhibition of binding by benzomorphans, 3-(3-hydroxyphenyl)-N-propylpiperidine and butaclamol, and the (+) enantiomers and alpha diastereomers of pentazocine and cyclazocine were more potent than their corresponding (-) enantiomers and beta diastereomers. The rank order of potency for the sigma reference agents to displace [3H](+)-pentazocine binding was similar to that reported using the [3H]sigma ligands dextromethorphan, 1,3-di(2-tolyl)guanidine and (+)-3-(3-hydroxyphenyl)-N-propylpiperidine. Haloperidol, (+)-pentazocine, (+)-3-(3-hydroxyphenyl)-N-propylpiperidine and rimcazole were competitive inhibitors of binding to the [3H](+)-pentazocine-defined sigma recognition site, suggesting that these different structural classes of compounds all bind to a single molecular entity.

Animals↗