Spiroperidol Binding Research Articles

Enduring changes in dopamine receptor cells of pups from drug administration to pregnant and nursing rats.

A decrease in specific [3H]spiroperidol binding to rat caudate tissue and a parallel decrease in sensitivity to apomorphine in eliciting stereotyped behavior was observed in the offspring of rat mothers treated with either haloperidol or alpha-methyl-p-tyrosine-methyl ester during pregnancy. In contrast, evidence of increased dopamine-receptor sensitivity was observed in the pups if haloperidol was administered to their mothers postpartum during nursing rather than during pregnancy.

Chronic lead treatment differentially affects dopamine synthesis in various rat brain areas

The effect of chronic dietary lead exposure on brain nigrostriatal, mesolimbic and mesocortial systems was studied. The results show no modification of the dopamine receptors measured either as dopamine sensitive adenylate cyclase or as [ 3H]spiroperidol binding. On the other hadn, dopamine synthesis seems to be reduced in striatum, unaffected in substantia nigra and increased in nucleus accumbens and in the frontal cortex. The increase of DA synthesis observed in some brain areas might be involved in determining the hyperactive behaviour that follows lead intoxication.

3H]Spiroperidol (Spiperone) Binding to a Putative Dopamine Receptor in Sheep and Steer Pituitary and Stalk Median Eminence*

The dopamine antagonist [3H]spiroperidol (spiperone) binds with high affinity to one class of sites in the sheep and steer anterior pituitary, posterior pituitary, and stalk median eminence. The specific binding in the anterior pituitary of the sheep satisfies all criteria studied for a receptor, including high affinity binding (dissociation constant = 0.85 nM for sheep and 0.38 nM for steer), saturability (sites = 343 fmol/mg protein for sheep and 210 fmol/mg for steer), temperature dependence, and reversibility. The rank order of potency of various agonists to compete with [3H]spiroperidol for the sites in the sheep anterior pituitary is consistent with interactions at a dopamine receptor (i.e. bromergocryptine > apomorphine > dopamine > norepinephrine ≥ epinephrine). Furthermore, this potency series parallels that seen for the inhibition of PRL secretion from the anterior pituitary in vitro. Dopamine metabolites, β-endorphin, TRH, and the catecholestrogen methoxyestrone did not compete for [3H]spiroper...

Studies on the stereoselective dopamine receptor blockade in the rat brain by rigid spiro amines

The effects of two series of tetracyclic spiro amines and of chlorpromazine, clozapine and sulpiride on ( 3H)-spiroperidol binding in various dopamine areas of the brain and on apomorphine induced stereotypies and hyperactivity was studied in rats. The two series of rigid spiro amines (racemates and enantiomers) were found to exhibit stereoselective effects on ( 3H)-spiroperidol binding and on apomorphine induced behaviours, thus providing evidence for stereospecific dopamine receptor blockade. Of the four enantiomers of the spiro amines only one (cis-(-)) showed a high potency, higher than that of chlorpromazine, clozapine and sulpiride. Sulpiride was a weak inhibitor of ( 3H)-spiroperidol binding and was less active in limbic areas than in the striatum. The potencies of the spiro amines as well as of chlorpromazine and clozapine in displacing ( 3H)-spiroperidol in the striatum and in the limbic dopamine system (nucleus accumbens and tuberculum olfactorium) correlated closely with their potencies in inhibiting apomorphine induced stereotypies and hyperactivity.

Dopamine receptors: Pharmacological and anatomical evidences indicate that two distinct dopamine receptor populations are present in rat striatum

( 3H)-haloperidol and ( 3H)-spiroperidol binding studies after kainate injection into the striatum indicate the presence of dopamine receptive sites not located on post-synaptic membranes. The majority of these dopamine “receptors” which are not associated to an adenylate cyclase appear to be localized on terminals of cortico-striatal neurons. On the other hand sulpiride, an antipsychotic drug which increases striatal dopamine synthesis, does not inhibit dopamine-stimulated adenylate cyclase either in vitro or in vivo. However sulpiride stereospecifically displaces ( 3H)-haloperidol from striatal binding sites.

3H]Haloperidol and [3H]spiroperidol binding in rat striatum during ageing.

3H]Haloperidol and [3H]spiroperidol binding in rat striatum during ageing.

3H]haloperidol and [ 3H]spiroperidol receptor binding after striatal injection of kainic acid

[ 3]Haloperidol and [ 3H]spiroperidol binding studies after kainate injection into the striatum indicate the presence of dopamine receptive sites not located on post-synaptic membranes. However, the physiological meaning of these “presynaptic” sites remains to be established.

Binding of opiates and endogenous opioid peptides to neuroleptic receptor sites in the corpus striatum

Some opiates with morphinan- and benzomorphan-structures possess affinities for neuroleptic receptors as revealed by their abilities to compete with 3H-spiroperidol for common binding sites in rat striatum in vitro (IC 50 in the range between 10 −6 and 10 −5M). The binding of these opiates to neuroleptic receptors appears to be of pharmacological significance, since in vivo studies in mice revealed a small but significant displacement of spiroperidol by high doses of the opiate antagonist levallorphan from specific binding sites in the striatum. In addition, there exists some correlation between the ability of opiates to bind to neuroleptic receptor sites in vitro and their potency to evoke “bizarre behavior” in rats in vivo . In contrast, a wide variety of other opiates having morphine-, morphinone- or oripavine-structure showed no affinity for neuroleptic binding sites in vitro (IC 50 greater than 10 −4 M). Of the opioid peptides (methionine-enkephalin, leucine-enkephalin and β-endorphin) none has an affinity for neuroleptic binding sites. A variety of other peptides were also investigated but did not interfere with spiroperidol binding. Only ACTH showed a moderate affinity for neuroleptic binding sites.

A comparative study of [ 3H] haloperidol and [ 3H] spiroperidol binding to receptors on rat cerebral membranes

FEBS LettersVolume 87, Issue 1 p. 152-156 Full-length articleFree Access A comparative study of [3H] haloperidol and [3H] spiroperidol binding to receptors on rat cerebral membranes First published: March 01, 1978 https://doi.org/10.1016/0014-5793(78)80155-0Citations: 41AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References [1] Hornykiewicz O., Brit. Med. Bull., 29, (1973), 172– 178. [2] Hornykiewicz O., Ann. Rev. Pharmacol. Toxicol., 17, (1977), 545– 559. [3] Seeman P., Biochem. Pharmacol., 26, (1977), 1741– 1748. [4] Burt D.R., Creese I., Snyder S.H., Mol. Pharmacol., 12, (1976), 800– 812. [5] Enna S.J., Bennett J.P. jr, Burt D.R., Creese I., Snyder S.H., Nature, 263, (1976), 338– 341. [6] Janssen P.A.J., Van Bever W.F.M., Curr. Develop. Psychopharmacol., 2, (1975), 165– 184. [7] Fields J.Z., Reisine T.D., Crawford D., Enna S.J., Yamamura H.I., Trans. Am. Soc. Neurochem., 8, (1977), 193– [8] Lindvall O., Bjorklund A., Divac I., E. Costa G.L. Gessa Non-striatal Dopaminergic Neurons (1977), Raven Press New York 39– 46. Citing Literature Volume87, Issue1March 01, 1978Pages 152-156 ReferencesRelatedInformation

Biogenic amine-stimulated adenylate cyclase and spiroperidol-binding sites in rabbit brain: evidence for selective loss of receptors with aging.

Evidence for selective decreases in biogenic amine receptor function with age in the rabbit has been obtained. Dopamine-stimulated adenylate cyclase activity in the striatum (caudate-putamen) of rabbit brain declined by about 50 percent as rabbits aged from less than 1 to 4 to 5 years of age. Similar decreases in transmitter-stimulated adenylate cyclase activity were found for histamine as well as for dopamine and norepinephrine in hypothalamus, frontal cortex and anterior limbic cortex. Isoproterenol-stimulated activity was also decreased with age in frontal cortex. These changes appeared to represent decreases in maximal response and not alteration in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and transmitter-independent (basal or Gpp(NH)p-stimulated) activity in each of the regions studied were not altered with age. Dopamine receptors in striatum directly assessed by measurement of [3H]-spiroperidol binding revealed a comparable decrease in the number of binding sites without change in ligand affinity. Preliminary data also indicated decreased spiroperidol binding sites in the cortical regions of older animals. These changes in striatum and cortex were evident in the absence of decreases in either dopamine content or choline acetylase activity, an activity presumed to be present in neurons containing dopamine receptors. It is proposed that selective age-dependent decreases in postsynaptic biogenic amine receptor content occur in the absence of, or independent from, neuronal cell loss, possibly by a mechanism involving receptor desensitization. These changes occur in the animal model in those brain regions which in man are thought to be of importance in the loss of cerebral function that is found with senscence.

Carotid body: structure and function.

Through an unfortunate error in make-up of the article “Carotid Body: Structure and Function,” by T. J. Biscoe, in the July issue of this journal, two sections of the review are out of order. To co...