Typical and atypical antipsychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain
- PMID: 2872945
- DOI: 10.1016/0361-9230(86)90181-4
Typical and atypical antipsychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain
Abstract
In thin sections of rat brain, [3H]spiperone binds to D2 sites in the basal ganglia (caudate-putamen, nucleus accumbens, olfactory tubercle) and S2 sites in the claustrum and motor cortex. The in vitro displacement of [3H]spiperone from these regions was quantified autoradiographically with the "atypical" neuroleptics clozapine and thioridazine, which ameliorate psychosis, a "typical" neuroleptic, haloperidol, which also induces extrapyramidal side effects, or with metoclopramide, which induces extrapyramidal side effects but is an ineffective antipsychotic. Whereas metoclopramide was equipotent at D2 sites, haloperidol was less potent and clozapine and thioridazine more potent by 2- to 3-fold at competing for D2 sites in the nucleus accumbens or olfactory tubercle than in the caudate-putamen. As measured autoradiographically or with tissue homogenates, clozapine, thioridazine, and five other atypical neuroleptics were 4- to 800-times more potent at competing for S2 sites in the frontal cortex than for D2 sites in the basal ganglia. A preference of atypical antipsychotics for D2 receptors in the nucleus accumbens and olfactory tubercle and for the S2 receptor may explain the relative lack of extrapyramidal side effects produced by these compounds.
Similar articles
-
Computer imaging and analysis of dopamine (D2) and serotonin (S2) binding sites in rat basal ganglia or neocortex labeled by [3H]spiroperidol.J Pharmacol Exp Ther. 1985 May;233(2):527-38. J Pharmacol Exp Ther. 1985. PMID: 3889277
-
Subchronic administration of clozapine, but not haloperidol or metoclopramide, decreases dopamine D2 receptor messenger RNA levels in the nucleus accumbens and caudate-putamen in rats.Neuroscience. 1996 May;72(1):99-104. doi: 10.1016/0306-4522(95)00540-4. Neuroscience. 1996. PMID: 8730709
-
Effects of acute and chronic treatments with clozapine and haloperidol on serotonin (5-HT2) and dopamine (D2) receptors in the rat brain.Brain Res. 1989 May 22;487(2):288-98. doi: 10.1016/0006-8993(89)90833-0. Brain Res. 1989. PMID: 2525063
-
Expression of the proneurotensin gene in the rat brain and its regulation by antipsychotic drugs.Ann N Y Acad Sci. 1992;668:54-69. doi: 10.1111/j.1749-6632.1992.tb27339.x. Ann N Y Acad Sci. 1992. PMID: 1361120 Review.
-
Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors.Neuropsychopharmacology. 1997 Feb;16(2):93-110; discussion 111-35. doi: 10.1016/S0893-133X(96)00187-X. Neuropsychopharmacology. 1997. PMID: 9015795 Review.
Cited by
-
Clozapine. A review of its pharmacological properties, and therapeutic use in schizophrenia.Drugs. 1990 Nov;40(5):722-47. doi: 10.2165/00003495-199040050-00007. Drugs. 1990. PMID: 2292234 Review.
-
Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats.J Neural Transm Gen Sect. 1990;82(2):93-109. doi: 10.1007/BF01245166. J Neural Transm Gen Sect. 1990. PMID: 1977417
-
A comparison of the effects of loxapine with ziprasidone and thioridazine on the release of dopamine and acetylcholine in the prefrontal cortex and nucleus accumbens.Psychopharmacology (Berl). 2003 May;167(3):315-23. doi: 10.1007/s00213-003-1418-x. Epub 2003 Mar 28. Psychopharmacology (Berl). 2003. PMID: 12664192
-
_target identification for CNS diseases by transcriptional profiling.Neuropsychopharmacology. 2009 Jan;34(1):18-54. doi: 10.1038/npp.2008.172. Epub 2008 Oct 15. Neuropsychopharmacology. 2009. PMID: 18923405 Free PMC article. Review.
-
Clozapine: an appraisal of its pharmacoeconomic benefits in the treatment of schizophrenia.Pharmacoeconomics. 1993 Aug;4(2):131-56. doi: 10.2165/00019053-199304020-00007. Pharmacoeconomics. 1993. PMID: 10146973
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
