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At least 145 records · Page 8Linked to original sources
PubMed1986

3H-spiperone binding in platelet membranes: a possible biological marker for schizophrenia.

High-affinity-specific 3H-spiperone binding to platelet membranes was carried out in 30 schizophrenic patients, without prior antipsychotic medication, fulfilling the Research Diagnostic Criteria, and in 30 matched control subjects. The psychosis was rated on the Modified Brief Psychiatric Rating Scale. Compared with healthy subjects, schizophrenic patients had significantly higher 3H-spiperone binding due to a lower dissociation constant (38%), i.e. increased affinity. No significant difference was observed in the maximum number of binding sites (Bmax) between the two groups. It is our contention that 3H-spiperone binding to platelets may be a biological marker for schizophrenia.

Adolescent↗
PubMed1988

Chronic uridine treatment reduces the level of [3H]spiperone-labelled dopamine receptors and enhances their turnover rate in striatum of young rats: relationship to dopamine-dependent behaviours.

The effect was studied of chronic uridine treatment on the recovery of striatal D-2 dopamine (DA) receptors after their irreversible blockade by N-ethoxycarbonyl-2-ethoxy-I,2-dihydroquinoline (EEDQ) in young (40 days old) and adult (14 months old) male rats using [3H]spiperone as radioligand. Chronic uridine treatment (15 mg kg-1 day-1, i.p., 14 days) causes a reduction of [3H]spiperone binding sites in striatum of young rats. This treatment also produces an increase in the rate of recovery of striatal [3H]spiperone-labelled DA receptors in young, but not in adult rats. Catalepsy and exploratory locomotor activity, two behaviours associated with blockade versus activation of DA receptors, were evaluated in the same rats. The behavioural recovery from the EEDQ-induced syndrome is more rapid in the young rats treated with uridine than in the saline-treated group. The behavioural recovery in old rats was not affected by chronic uridine treatment. Thus, in young rats the pyrimidine nucleoside uridine may modulate the steady state and the turnover rate of striatal D-2 DA receptors.

Adrenergic alpha-Antagonists↗
PubMed1982

Central injections of spiperone and GABA: attenuation of angiotensin II stimulated thirst.

This study investigated the effects of injecting spiperone or gamma-aminobutyric acid (GABA) into the brain on drinking induced by angiotensin II injected into a lateral cerebral ventricle of the rat. Injections of 12.5 pM of angiotensin II elicited water intakes averaging 10 mL in 15 min with latencies of less than 3 min. Spiperone, a dopamine antagonist injected into the nucleus accumbens produced dose-dependent reductions in water intake and number of laps while increasing the latency to drink. Injections of GABA into the ventral tegmental area produced dose-dependent reductions in water intake and number of laps without altering latency to drink or lap volume. GABA injected into the globus pallidus reduced drinking in a manner similar to that described for spiperone injected into the nucleus accumbens when angiotensin II was the dipsogenic agent but was totally without effect on drinking induced by carbachol injections. These results indicate that a proposed neuronal circuit composed of GABA input to ventral tegmental area neurons, dopamine input from the ventral tegmental area to nucleus accumbens neurons, and subsequent GABA input from the nucleus accumbens to globus pallidus neurons may interact with the goal-directed behaviour, drinking, elicited by central angiotensin II administration. Further, they provide evidence that this neuronal circuit may be part of a functional interface for response initiation.

Angiotensin II↗
PubMed1995

Specific [3H]spiperone binding sites in the pituitary of rainbow trout (Oncorhynchus mykiss) and goldfish (Carassius auratus).

Dopamine, a catecholamine neurohormone, modulates pituitary hormone release in teleost fishes and other vertebrates. The existence and binding parameters of a pituitary dopamine-neuroleptic receptor from trout were examined and compared with those from goldfish. Pituitary homogenate was incubated with [3H]spiperone (D2 antagonist) under several experimental paradigms; incubations were terminated by filtration and bound 3H radioactivity was assessed by liquid scintillation spectroscopy. Specific binding of [3H]spiperone was tissue dependent. Equilibrium displacement analyses using domperidone (D2 antagonist) indicated a single class of binding site (LIGAND) with Kd = 2.49 +/- 0.89 microM and a capacity of 3.10 +/- 0.45 nmol/mg protein; the goldfish Kd and capacity were both significantly (p < 0.05) larger: Kd = 4.63 +/- 0.30 microM and capacity = 20.66 +/- 2.03 nmol/mg protein. The Kd and capacity for the trout pars distalis (2.45 +/- 0.33 microM and 3.27 +/- 0.24 nmol/mg protein, respectively) did not differ significantly (p < 0.05) from that of the neurointermediate lobe (2.50 +/- 0.08 microM and 3.58 +/- 0.56 nmol/mg protein, respectively). Dopamine D2 receptor ligands differentially displaced [3H]spiperone from the trout pituitary, while D1 ligands, a D4 ligand, and a 5-hydroxytryptamine (5HT2) receptor antagonist had only small nonspecific effects. Comparison of the trout and goldfish pituitary dopamine-neuroleptic receptor indicates conservation of receptor affinity (Kd); however, differences in receptor numbers and in the distribution of receptors between the pars distalis and neurointermediate lobe in the two species may be due in part to species or developmental differences, and may reflect differences in the role(s) and degrees of influence of dopamine in these fishes.

Animals↗
PubMed1989

Ovariectomy permits progesterone to increase the binding of [3H]spiperone to the anterior pituitary gland in estrogen-primed rats.

The binding of the dopamine (DA) D2 antagonist spiperone to DA receptors in the anterior pituitary gland was evaluated in intact and ovariectomized (OVX) estrogen-primed rats in which circulating levels of progesterone (P) were varied. Nembutal (PB; 35 mg/kg, ip) was administered at 1130 h to intact proestrous animals to prevent the LH-stimulated release of ovarian P. Two hours later some of these intact rats were QVX to remove the endogenous ovarian steroids. Both intact and OVX rats were given exogenous P. All rats were killed on the following morning, and adenohypophysial binding of [3H]spiperone was evaluated at a saturating concentration. The binding in intact PB-blocked rats that received P was only 52% of that in PB-blocked rats that were OVX and received P. The binding of [3H]spiperone in PB-treated rats that were OVX and given P did not differ statistically from that in normal estrous rats. A parallel experiment was conducted on other rats that had been OVX 7 days before the sc implantation (on day 0) of Silastic capsules containing estradiol (E2). Two days later (day 2), some of these rats were injected with Nembutal at 1130 h. Two hours later, the E2 capsules of some rats were removed to simulate ovariectomy; Silastic capsules containing P were implanted into both E2-bearing and non-E2-bearing rats. All rats were killed the following morning (day 3), and the density of adenohypophysial DA receptors was assessed. Binding densities were greatest in rats bearing both E2 and P capsules and in rats from which E2 capsules were removed and replaced with P capsules. We conclude that treatment of OVX rats with the sequential combination of E2 and P increases the density of DA receptors in the anterior pituitary gland. However, in intact rats an additional ovarian product prevents the P-induced increase in the density of adenohypophysial DA receptors.

Animals↗
PubMed1991

The effect of haloperidol, spiperone and dantrolene on the concentrations of creatine phosphate, ATP and lactate in brain and skeletal muscle of the rat during halothane anesthesia.

The concentrations of creatine phosphate, ATP and lactate were measured in the brain and skeletal muscle of rats under halothane anesthesia (1 to 2% in oxygen) and in animals either premedicated with haloperidol or spiperone (200 mg kg-1 and 2 mg kg-1) or treated with dantrolene (860 mg kg-1). Haloperidol and spiperone had no effect on ATP or lactate in skeletal muscle, but caused more than a 30% increase in the concentration of creatine phosphate (p less than 0.01). With dantrolene, an 80% increase in creatine phosphate (p less than 0.0001) and a significant decrease in lactate (p less than 0.0001) were found. Haloperidol caused a significant decrease in brain creatine phosphate concentration (p less than 0.05) while at a dosage of 2 mg kg-1, the ATP concentration was higher (p less than 0.05). Spiperone (2 mg kg-1) caused a 19% increase in creatine phosphate (p less than 0.005) as well as a significant decrease in lactate (p less than 0.005). Dantrolene had no significant effect on the concentration of any brain metabolite. Our results indicate that the effect of anesthetics on the concentration of energy metabolites in tissues can be influenced by drug treatment, which may have implications in the choice of an anesthetic regimen to be used in tissue harvesting.

Adenosine Triphosphate↗
PubMed1983

Temperature-dependent 5-hydroxytryptamine (5-HT)-sensitive [3H]spiperone binding to rat cortical membranes: regulation by guanine nucleotide and antidepressant treatment.

5-Hydroxytryptamine (5-HT)-sensitive binding of [3H]spiperone to rat cortical membranes was examined at 22 degrees C and 37 degrees C. At the lower temperature a significantly higher density of specific sites with identical affinity for [3H]spiperone (0.15 nM) was observed. Furthermore, a proportion of sites at 22 degrees C, although not at 37 degrees C, possessed high affinity for 5-HT and these were apparently converted to low affinity sites by GTP (100 microM). Examination of the apparent affinities of the 5-HT derivatives 5-methoxytryptamine, 5,6-dihydroxytryptamine and tryptamine revealed differences in the potencies of these analogs that were particularly evident for the high affinity proportion of sites observed at 22 degrees C. Subchronic treatment of rats with the antidepressants mianserin and iprindole reduced the density of [3H] spiperone binding sites when assays were performed at either temperature. However, antidepressant treatment appeared to preferentially reduce the number of sites that possess high affinity for 5-HT.

Animals↗
PubMed1982

Increased 3H-spiperone binding sites in mesolimbic area related to methamphetamine-induced behavioral hypersensitivity.

The specific 3H-spiperone binding to membrane homogenates of the striatum, mesolimbic area, and frontal cortex was examined in two groups of rats pretreated once daily with saline or 4 mg/kg of methamphetamine (MAP) for 14 days. At 7 days following cessation of chronic pretreatment, all rats received an injection of 4 mg/kg of MAP and were decapitated 1 hr after the injection. In the chronic saline-pretreatment group, the single administration of MAP induced significant changes in the number (Bmax) of specific 3H-spiperone binding sites (a decrease in the striatum and an increase in the mesolimbic area and frontal cortex), but no significant changes in the affinity (KD) in any brain area. The chronic MAP pretreatment markedly augmented the changes in Bmax in the striatum and mesolimbic area. The increase in specific 3H-spiperone binding sites in the mesolimbic area is discussed in relation to MAP-induced behavioral hypersensitivity.

Animals↗
PubMedDate not supplied

[The binding of 3H-spiperone to lymphocytes in patients with schizophrenia and first-degree relatives: in search of a genetic marker].

3H-spiperone binding of lymphocytes has been studied and proposed to be a useful vulnerability marker for certain subtypes of schizophrenia. The binding of 3H-spiperone into lymphocytes was studied in 22 schizophrenics, 19 unaffected relatives and 8 healthy subjects. Binding assay was performed, incubating lymphocytes with 0.04 to 0.4 mM of 3H-spiperone. Non-specific binding was measured with 10 mM haloperidol. At the end the lymphocytes were homogenized. The results show a significant (p < 0.01) lower affinity (high Kd values) in drug naive schizophrenics compared with the controls. No differences were found in the binding capacity (Bmax) of both schizophrenic groups compared with control subjects. The results cannot offer us a reliable biological marker for schizophrenia. The increase of the number of subjects is suggested.

Adult↗
PubMed1997

Decreased [18F]spiperone binding in putamen in idiopathic focal dystonia.

In this study we have investigated the pathophysiology of two idiopathic focal dystonias: hand cramp with excessive cocontractions of agonist and antagonist hand or forearm muscles during specific tasks, such as writing, and facial dystonia manifested by involuntary eyelid spasms (blepharospasm) and lower facial and jaw spasms (oromandibular dystonia). We used positron emission tomography (PET) to measure the in vivo binding of the dopaminergic radioligand [18F]spiperone in putamen in 21 patients with these two focal dystonias and compared the findings with those from 13 normals. We measured regional cerebral blood flow and blood volume in each subject as well as the radiolabeled metabolites of [18F]spiperone in arterial blood. A stereotactic method of localization, independent of the appearance of the images, was used to identify the putamen in all of the PET images. We analyzed the PET and arterial blood data with a validated nonsteady-state tracer kinetic model representing the in vivo behavior of the radioligand. An index of binding called the combined forward rate constant was decreased by 29% in dystonics, as compared with normals (p < 0.05). There were no significant differences between dystonics and normals in regional blood flow, blood volume, nonspecific binding, permeability-surface area product of [18F]spiperone or the dissociation rate constant. These findings are consistent with a decrease of dopamine D2-like binding in putamen and are the first demonstration of a receptor abnormality in idiopathic dystonia. These results have important implications for the pathophysiology of dystonia as well as for function of the basal ganglia.

Adult↗
PubMed1998

Influence of SCH23390 and spiperone on the expression of conditioned place preference induced by d-amphetamine or cocaine in the rat.

The present study investigated the effects of selective dopamine D1 and D2 receptor antagonists, SCH23390 and spiperone, on the expression of conditioned place preference (CPP) induced by either d-amphetamine or cocaine. The CPP protocol consisted of three phases: pre-conditioning exploration, conditioning, and a post-conditioning test. The data indicated that CPP was significantly induced by intraperitoneal injection of either d-amphetamine (2 mg/kg) or cocaine (10 mg/kg). The expression of d-amphetamine CPP was significantly inhibited by SCH23390 (0.08, 0.16 mg/kg) and spiperone (0.15 mg/kg) when given alone before the post-conditioning test session. In contrast, such pretreatment to produce antagonistic effects was not observed for cocaine CPP. However, the expression of cocaine CPP was significantly attenuated by a combination of SCH23390 and spiperone administered prior to the test session. These data indicate that the rewarding properties of d-amphetamine and cocaine as expressed under the CPP task may depend upon different neural substrates. The degrees of D1 and D2 receptors involved in mediating the expression of CPP induced by d-amphetamine and cocaine are different.

Animals↗
PubMed1983

Conformational study of two polymorphs of spiperone: possible consequences on the interpretation of pharmacological activity.

A second polymorph of spiperone, 8-[3-(p-fluorobenzoyl)-propyl]-1-phenyl-1,3,8-triazaspiro[4,5] decan-4-one, has been isolated and characterized by thermal analysis and IR spectrometry. Its structure was solved by X-ray diffraction analysis. The results are compared with those previously obtained on spiperone, the main difference being in the conformation of the side chain and in the nature of the hydrogen bonding.

Butyrophenones↗
PubMed1989

3H-spiperone binding sites in post-mortem brains from schizophrenic patients: relationship to neuroleptic drug treatment, abnormal movements, and positive symptoms.

In post-mortem putamen samples from 27 schizophrenics and 27 controls D2 receptors were measured by Scatchard analysis using 3H-spiperone as a ligand. Maximum number of binding sites (Bmax) and apparent dissociation constant (KD) were significantly increased only in patients in whom neuroleptic medication had been given within a three-month period before death. When the neuroleptic medication had been withdrawn at least 3 month before death, there was a slight, but not significant, reduction in Bmax values and unchanged KD values. Withdrawal of neuroleptic drugs was followed by a normalization of the KD values within 2 weeks and a slower reduction of Bmax values. There were 6 schizophrenic patients with mainly positive schizophrenic symptoms and 17 patients with mainly negative symptoms; positive schizophrenic symptoms were not related to higher Bmax values. There was no difference in 3H-spiperone binding between patients with and without movement disorders (tardive dyskinesia or extrapyramidal symptoms).

Aged↗
PubMed1985

The effect of cholecystokinin octapeptide on rat striatal 3H spiperone binding.

In the rat striatum sulphated CCK8 has no significant effect on equilibrium binding of 3H-spiperone but has a considerable, although transient, effect under non-equilibrium conditions. Under non-equilibrium conditions (during the association phase of ligand binding) and at high ligand concentrations (1 nM), CCK8 displaces specific binding and at low ligand concentrations (0.1 nM) CCK8 enhances specific binding. CCK8 has no effect on 3H-spiperone dissociation kinetics.

Animals↗
PubMed1982

Ovine prolactin administration modifies [3H]spiperone binding to striatal membranes of rabbits.

The binding of [3H]spiperone to striatal membranes from rabbit brain was evaluated in untreated male and female and in female rabbits after treatment with ovine prolactin (1 mg/kg, i.v.) or with saline. Unsubstantial differences were found between male and female striatal [3H]spiperone binding sites, both in affinity and density. Ovine prolactin treatment induced an increased binding site density and a lower affinity than occurred in the female controls. These results appear similar to those obtained after chronic neuroleptic treatment and confirm that prolactin is able to affect the dopaminergic neurotransmission system.

Animals↗
PubMed1986

Chronic treatment with L-DOPA, but not bromocriptine induces dyskinesia in MPTP-parkinsonian monkeys. Correlation with [3H]spiperone binding.

A group of 5 monkeys developed a severe parkinsonian syndrome after intravenous administration of the toxin MPTP. One remained untreated while two animals were treated daily for 5 months with supramaximal doses of Sinemet and two with bromocriptine orally. Both drugs relieved the parkinsonian symptoms but the animals on Sinemet developed after 2 weeks prominent lingual dyskinesia which remained visible after each dose until the end of the experiment. In the two animals on bromocriptine no dyskinesia was observed. After sacrifice, the levels of dopamine and [3H]spiperone binding were studied bilaterally in the anterior and posterior caudate nucleus, anterior and posterior putamen and in the nucleus accumbens. The loss of dopamine was equivalent in the Sinemet and the bromocriptine treated animals (more than 90%) and there was a complete disappearance of the substantia nigra pars compacta. In all structures studied, the Bmax for [3H]spiperone binding was on average 10% higher in the Sinemet than in the bromocriptine-treated animals. We therefore believe that L-DOPA and bromocriptine affect denervated postsynaptic dopamine receptors differently, that bromocriptine is less likely to induce agonist supersensitivity and that this probably explains the lesser tendency to induce dyskinesia after chronic treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1979

Inhibition of in vivo 3H-spiperone binding by the proposed antipsychotic Des-Tyr1-gamma-endorphin.

The proposed antipsychotic neuropeptide des-tyrosine1-gamma-endorphin (DT gamma E, beta LPH62,77) inhibits in vivo 3H-spiperone binding in the hypothalamus, corpus striatum and mesolimbic areas of rat brain. The neuroleptic drug haloperidol produces similar effects in these areas as well as in frontal cortex, but is considerably more potent than DT gamma E. Correspondingly, haloperidol produces postural and motor abnormalities not seen with DY gamma E. These data together with the results from previous in vitro studies suggest DT gamma E might act indirectly, having a selective neuroleptic-like action at 3H-spiperone binding sites.

Animals↗
PubMed1984

Interaction of dihydroxy-2-aminotetralin derivatives at sites labelled with [3H]clonidine, [3H]prazosin and [3H]spiperone in rat brain membranes.

The interactions of 5,6- and 6,7-dihydroxy derivatives of 2-aminotetralin with [3H]clonidine and [3H]prazosin as well as with [3H]spiperone binding sites in rat cerebral cortex membrane preparations were investigated. The hydroxy derivatives of 2-aminotetralin tested showed significant interaction with [3H]clonidine as well as with [3H]peiperone binding sites while for [3H]prazosin binding site these agents appeared virtually inactive. For interaction with [3H]clonidine binding site 6,7-dihyroxy substitutions impart greater potency that 5,6-dihydroxy substitutions and N-alkyl substitutions either make no differece or reduce the affinity of these compounds. N-alkyl substitutions, however, markedly enhance the affinity of 5,6-dihydroxy derivatives for interaction with [3H]spiperone binding site. The results suggest that some hydroxy derivatives of aminotetralin have significant interaction with both central alpha 2-adrenoceptor and D2-dopamine receptor systems.

Animals↗