Selective D1- and D2-dopamine Receptor Blockade Both Induces Akathisia in Humans--a PET Study with [11C]SCH 23390 and [11C]raclopride

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1992 Jan 1

PMID 1534178

Citations 18

Authors

L Farde

Affiliations

Soon will be listed here.

Abstract

Pharmacological effects were recorded and time course for receptor binding in brain was followed by positron emission tomography after IV injection of the selective D1-dopamine receptor antagonist SCH 23390 in four healthy subjects in doses of 310-810 micrograms. Akathisia, the syndrome of motor restlessness, appeared after the three highest doses. The akathisia was transient and occurred only when [11C]SCH 23390 binding in the basal ganglia was at a high level with a central D1-dopamine receptor occupancy of 45-59%. The D2-dopamine receptor antagonist [11C]raclopride was injected IV into 20 healthy subjects and 13 schizophrenic patients. Akathisia appeared in 14 healthy subjects and 7 patients and coincided with maximal [11C]raclopride binding in the basal ganglia. The findings for [11C]raclopride and [11C]SCH 23390 are the first demonstration of a relationship between time courses for radioligand binding in the human brain and simultaneously induced pharmacological effects.

Citing Articles

D1-Dopamine Receptor Availability in First-Episode Neuroleptic Naive Psychosis Patients.

Stenkrona P, Matheson G, Halldin C, Cervenka S, Farde L Int J Neuropsychopharmacol. 2019; 22(7):415-425.

PMID: 30958880 PMC: 6600463. DOI: 10.1093/ijnp/pyz017.

Connectome and molecular pharmacological differences in the dopaminergic system in restless legs syndrome (RLS): plastic changes and neuroadaptations that may contribute to augmentation.

Earley C, Uhl G, Clemens S, Ferre S Sleep Med. 2016; 31:71-77.

PMID: 27539027 PMC: 5191980. DOI: 10.1016/j.sleep.2016.06.003.

PET molecular imaging in stem cell therapy for neurological diseases.

Wang J, Tian M, Zhang H Eur J Nucl Med Mol Imaging. 2011; 38(10):1926-38.

PMID: 21698414 DOI: 10.1007/s00259-011-1860-7.

Antidepressant and Antipsychotic Drugs.

Krystal A Sleep Med Clin. 2011; 5(4):571-589.

PMID: 21499530 PMC: 3076958. DOI: 10.1016/j.jsmc.2010.08.010.

A cross-validation study on the relationship between central D2 receptor occupancy and serum perphenazine concentration.

Talvik M, Nordstrom A, Larsen N, Jucaite A, Cervenka S, Halldin C Psychopharmacology (Berl). 2004; 175(2):148-53.

PMID: 15007534 DOI: 10.1007/s00213-004-1802-1.

References

Van Putten T, MAY P, Marder S, Wittmann L . Subjective response to antipsychotic drugs. Arch Gen Psychiatry. 1981; 38(2):187-90. DOI: 10.1001/archpsyc.1981.01780270073010. View

FREYHAN F . Psychomotility and parkinsonism in treatment with neuroleptic drugs. AMA Arch Neurol Psychiatry. 1957; 78(5):465-72. DOI: 10.1001/archneurpsyc.1957.02330410029003. View

Barnes T, Braude W . Akathisia variants and tardive dyskinesia. Arch Gen Psychiatry. 1985; 42(9):874-8. DOI: 10.1001/archpsyc.1985.01790320042006. View

Litton J, Bergstrom M, Eriksson L, Bohm C, Blomqvist G, Kesselberg M . Performance study of the PC-384 positron camera system for emission tomography of the brain. J Comput Assist Tomogr. 1984; 8(1):74-87. DOI: 10.1097/00004728-198402000-00016. View

Farde L, Wiesel F, Stone-Elander S, Halldin C, Nordstrom A, Hall H . D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry. 1990; 47(3):213-9. DOI: 10.1001/archpsyc.1990.01810150013003. View

Kebabian J, Petzold G, Greengard P . Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the "dopamine receptor". Proc Natl Acad Sci U S A. 1972; 69(8):2145-9. PMC: 426888. DOI: 10.1073/pnas.69.8.2145. View

Barnes T . A rating scale for drug-induced akathisia. Br J Psychiatry. 1989; 154:672-6. DOI: 10.1192/bjp.154.5.672. View

Adler L, Angrist B, Reiter S, Rotrosen J . Neuroleptic-induced akathisia: a review. Psychopharmacology (Berl). 1989; 97(1):1-11. DOI: 10.1007/BF00443404. View

Casey D . Dopamine D1 (SCH 23390) and D2 (haloperidol) antagonists in drug-naive monkeys. Psychopharmacology (Berl). 1992; 107(1):18-22. DOI: 10.1007/BF02244960. View

10.

Halldin C, Stone-Elander S, Farde L, Ehrin E, Fasth K, Langstrom B . Preparation of 11C-labelled SCH 23390 for the in vivo study of dopamine D-1 receptors using positron emission tomography. Int J Rad Appl Instrum A. 1986; 37(10):1039-43. DOI: 10.1016/0883-2889(86)90044-4. View

11.

Frost J, Smith A, Kuhar M, Dannals R, Wagner Jr H . In vivo binding of 3H-N-methylspiperone to dopamine and serotonin receptors. Life Sci. 1987; 40(10):987-95. DOI: 10.1016/0024-3205(87)90321-3. View

12.

Farde L, Eriksson L, Blomquist G, Halldin C . Kinetic analysis of central [11C]raclopride binding to D2-dopamine receptors studied by PET--a comparison to the equilibrium analysis. J Cereb Blood Flow Metab. 1989; 9(5):696-708. DOI: 10.1038/jcbfm.1989.98. View

13.

Bergstrom M, Boethius J, Eriksson L, Greitz T, Ribbe T, WIDEN L . Head fixation device for reproducible position alignment in transmission CT and positron emission tomography. J Comput Assist Tomogr. 1981; 5(1):136-41. DOI: 10.1097/00004728-198102000-00027. View

14.

Cortes R, Camps M, Gueye B, Probst A, Palacios J . Dopamine receptors in human brain: autoradiographic distribution of D1 and D2 sites in Parkinson syndrome of different etiology. Brain Res. 1989; 483(1):30-8. DOI: 10.1016/0006-8993(89)90031-0. View

15.

Sokoloff P, Giros B, Martres M, Bouthenet M, Schwartz J . Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 1990; 347(6289):146-51. DOI: 10.1038/347146a0. View

16.

Farde L, Hall H, Ehrin E, Sedvall G . Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science. 1986; 231(4735):258-61. DOI: 10.1126/science.2867601. View

17.

Joyce J, Lexow N, Bird E, Winokur A . Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington's disease and schizophrenia. Synapse. 1988; 2(5):546-57. DOI: 10.1002/syn.890020511. View

18.

Hall H, Farde L, Sedvall G . Human dopamine receptor subtypes--in vitro binding analysis using 3H-SCH 23390 and 3H-raclopride. J Neural Transm. 1988; 73(1):7-21. DOI: 10.1007/BF01244618. View

19.

Seeman P, Lee T, Wong K . Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature. 1976; 261(5562):717-9. DOI: 10.1038/261717a0. View

20.

Hyttel J . SCH 23390 - the first selective dopamine D-1 antagonist. Eur J Pharmacol. 1983; 91(1):153-4. DOI: 10.1016/0014-2999(83)90381-3. View