BL-1020, a novel antipsychotic candidate with GABA-enhancing effects: D2 receptor occupancy study in humans

European Neuropsychopharmacology

Volumn 19, Issue 12, 2009, Pages 841-850

  Appel, Lieuwe ^a   Geffen, Yona ^b   Heurling, Kerstin ^a   Eriksson, Catarina ^c   Antoni, Gunnar ^a   Kapur, Shitij ^d  

^a BIACORE AB   (Sweden)

^b BIOLINERX LTD   (Israel)

^c IQVIA   (United States)

^d KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Antipsychotics; Dopamine 2 receptors; GABA; Perphenazine; PET; Schizophrenia

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID 2 [4 [3 (2 CHLOROPHENOTHIAZINE 10 YL)PROPYL]PIPERIZIN 1 YL]ETHYL ESTER; BL 1020; CARBON 11; DOPAMINE 2 RECEPTOR; NEUROLEPTIC AGENT; PERPHENAZINE; PROLACTIN; RACLOPRIDE; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIZZINESS; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG SAFETY; ELECTROCARDIOGRAPHY; EPISTAXIS; FATIGUE; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; MUSCLE SPASM; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; POLYURIA; POSITRON EMISSION TOMOGRAPHY; PREDICTION; PRIORITY JOURNAL; RECEPTOR BLOCKING; RECEPTOR OCCUPANCY; RHINOPHARYNGITIS; SIDE EFFECT; SINGLE DRUG DOSE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; VITAL SIGN; VOLUNTEER;

ADULT; ANTIPSYCHOTIC AGENTS; BRAIN; BRAIN MAPPING; CARBON RADIOISOTOPES; DOSE-RESPONSE RELATIONSHIP, DRUG; GAMMA-AMINOBUTYRIC ACID; HUMANS; MALE; PERPHENAZINE; POSITRON-EMISSION TOMOGRAPHY; PROLACTIN; PROTEIN BINDING; RACLOPRIDE; RECEPTORS, DOPAMINE D2; TIME FACTORS; YOUNG ADULT;

EID: 70350413631     PISSN: 0924977X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.euroneuro.2009.07.009     Document Type: Article

References (25)

1. Andersson J.L.R. A rapid and accurate method to realign PET scans utilizing image edge transformation. J. Nucl. Med. 36 (1995) 657-669
2. Benes F.M., Vincent S.L., and Molloy R. Dopamine-immunoreactive axon varicosities form nonrandom contacts with GABA-immunoreactive neurons of rat medial prefrontal cortex. Synapse 15 (1993) 285-295
3. Carlsson A., Waters N., Holm-Waters S., Tedroff J., Nilsson M., and Carlsson M.L. Interactions between monoamines, glutamate and GABA in schizophrenia, new evidence (Review). Annu. Rev. Pharmacol. Toxicol. 41 (2001) 237-260
4. Dahl-Puustinen M.L., Lidén A., Alm C., Nordin C., and Bertilsson L. Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings. Clin. Pharm. Ther. 46 (1989) 78-81
5. Farde L., Wiesel F.A., Halldin C., and Sedvall G. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch. Gen. Psychiatry 45 (1988) 71-76
6. Farde L., Nordström A.L., Wiesel F.A., Pauli S., Halldin C., and Sedvall G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch. Gen. Psychiatry 49 (1992) 538-544
7. Geffen Y., Nudelman A., Gil-Ad I., Rephaeli A., Huang M., Savitsky K., Klapper L., Winkler I., Meltzer H.Y., and Weizman A. BL-1020, a novel antipsychotic drug with GABAergic activity and low catalepsy, is efficacious in a rat model of schizophrenia. Eur. Neuropsychopharmacol. 19 (2009) 1-13
8. Guidotti A., Auta J., Davis J.M., Dong E., Grayson D.R., Veldic M., Zhang X., and Costa E. GABAergic dysfunction in schizophrenia, new treatment strategies on the horizon (Review). Psychopharmacology 180 (2005) 191-205
9. Hall H., Farde L., Halldin C., Högberg T., Larsson S., and Sedvall G. Imaging of dopamine receptors using PET and SPECT (Review). Neurochem. Int. 20 Suppl (1992) 329S-333S
10. Hall H., Sedvall G., Magnusson O., Kopp J., Halldin C., and Farde L. Distribution of D1 and D2 dopamine receptors, and dopamine and the metabolites in the human brain. Neuropsychopharmacology 11 (1994) 245-256
11. Jerling M., Dahl M.L., Åberg-Wistedt A., Liljenberg B., Landell N.E., Bertilsson L., and Sjöqvist F. The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol. Clin. Pharm. Ther. 59 (1996) 423-428
12. 2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study. Life Sci. 57 (1995) 103-107
13. Kapur S., Zipursky R.B., Jones C., Remington G., and Houle S. Relationship between dopamine D (2) occupancy, clinical response, and side effects: a double blind PET study of first-episode schizophrenia. Am. J. Psychiatry 157 (2000) 514-520
14. Karler R., Calder L.D., Thai D.K., and Bedingfield J.B. The role of dopamine in the mouse frontal cortex: a new hypothesis of behavioral sensitization to amphetamine and cocaine. Pharmacol. Biochem. Behav. 61 (1998) 435-443
15. Kuriyama K., and Sze P.Y. Blood-brain barrier to H3-gamma-aminobutyric acid in normal and amino oxyacetic acid-treated animals. Neuropharmacology 10 (1971) 103-108
16. Lammertsma A.A., and Hume S.P. Simplified reference tissue model for PET receptor studies. Neuroimage 4 (1996) 153-158
17. Lieberman J.A., Stroup T.S., McEvoy J.P., Swartz M.S., Rosenheck R.A., Perkins D.O., Keefe R.S., Davis S.M., Davis C.E., Lebowitz B.D., Severe J., Hsiao J.K., and Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353 (2005) 1209-1223
18. Lingjaerde O., Ahlfors U.G., Bech P., Dencker S.J., and Elgen K. The UKU Side Effect Rating Scale. A new comprehensive rating scale for psychotropic drugs, and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatrica Scandinavica Suppl 334 (1987) 1-100
19. 11C]raclopride binding in healthy young adults and schizophrenic patients - reliability and age effects. Hum. Psychopharmacology 7 (1992) 157-165
20. Nordström A.L., Farde L., Wiesel F.A., Forslund K., Pauli S., Halldin C., and Uppfeldt G. Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: A double-blind PET study of schizophrenic patients. Biol. Psychiatry 33 (1993) 227-235
21. Nudelman A., Gil-Ad I., Shpaisman N., Terasenko I., Ron H., Savitsky K., Geffen Y., Weizman A., and Rephaeli A. A mutual prodrug ester of GABA and perphenazine exhibits antischizophrenic efficacy with diminished extrapyramidal effects. J. Med. Chem. 51 (2008) 2858-2862
22. 2A receptor occupancy in schizophrenic patients. Am. J. Psychiatry 156 (1999) 869-875
23. Shukla V.K., Garg S.K., Mathur V.S., and Kulkarni S.K. GABAergic, dopaminergic and cholinergic interactions in perphenazine-induced catatonia in rats. Arch. Int. Pharmacodyn. Ther. 278 (1985) 236-248
24. Talvik M., Nordström A.L., Larsen N.E., Jucaite A., Cervenka S., Halldin C., and Farde L. A cross-validation study on the relationship between central D2 receptor occupancy and serum perphenazine concentration. Psychopharmacology 175 (2004) 148-153
25. Wassef A., Baker J., and Kochan L.D. GABA and schizophrenia, a review of basic science and clinical studies. J. Clin. Psychopharmacology 23 (2003) 601-640