A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia

Schizophrenia Research

Volumn 93, Issue 1-3, 2007, Pages 42-50

  George, Mark S ^a   Molnar, Christine E ^a   Grenesko, Emily L ^a   Anderson, Berry ^a   Mu, Qiwen ^a   Johnson, Kevin ^a   Nahas, Ziad ^a   Knable, Michael ^b   Fernandes, Prabhavathi ^c   Juncos, Jorge ^d   Huang, Xuemei ^e   Nichols, David E ^f   Mailman, Richard B ^e  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b Stanley Medical Research Institute   (United States)

^c Formerly of DarPharma Inc   (United States)

^d EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^f PURDUE UNIVERSITY   (United States)

Author keywords

Cognition; D1 dopamine agonists; D1 dopamine receptors; Dementia; Dopamine; Schizophrenia

Indexed keywords

DAR 0100; DIHYDREXIDINE; DOPAMINE 1 RECEPTOR STIMULATING AGENT; GADOLINIUM; PLACEBO; UNCLASSIFIED DRUG; DOPAMINE 1 RECEPTOR; DOPAMINE RECEPTOR STIMULATING AGENT; NEUROLEPTIC AGENT; OXYGEN; PHENANTHRIDINE DERIVATIVE;

ADULT; ARTICLE; BLOOD SAMPLING; BODY FLUSHING; BRAIN PERFUSION; CLINICAL ARTICLE; CLINICAL TRIAL; COGNITION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; FEMALE; FLUSHING; FUNCTIONAL MAGNETIC RESONANCE IMAGING; HEADACHE; HOSPITALIZATION; HUMAN; HYPERHIDROSIS; IMAGE ANALYSIS; INJECTION SITE IRRITATION; INJECTION SITE PAIN; LOW DRUG DOSE; MALE; NAUSEA; NEGATIVE SYNDROME; NEUROIMAGING; OUTPATIENT; OXYGEN BLOOD LEVEL; PILOT STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SCHIZOPHRENIA; SIDE EFFECT; SINGLE DRUG DOSE; SKIN TINGLING; TASK PERFORMANCE; TREMOR; VOMITING; WORKING MEMORY; XEROSTOMIA; BLOOD; BLOOD FLOW; BRAIN; DOSE RESPONSE; DRUG COMBINATION; DRUG POTENTIATION; IMAGE PROCESSING; MIDDLE AGED; NEUROPSYCHOLOGICAL TEST; NUCLEAR MAGNETIC RESONANCE IMAGING; PHYSIOLOGY; PSYCHOLOGICAL RATING SCALE; SHORT TERM MEMORY; SUBCUTANEOUS DRUG ADMINISTRATION; TREATMENT OUTCOME; VASCULARIZATION;

ADULT; ANTIPSYCHOTIC AGENTS; BRAIN; CROSS-OVER STUDIES; DOPAMINE AGONISTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; INJECTIONS, SUBCUTANEOUS; MAGNETIC RESONANCE IMAGING; MALE; MEMORY, SHORT-TERM; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; OXYGEN; PHENANTHRIDINES; PILOT PROJECTS; PSYCHIATRIC STATUS RATING SCALES; RECEPTORS, DOPAMINE D1; REGIONAL BLOOD FLOW; SCHIZOPHRENIA; TREATMENT OUTCOME;

EID: 34249319444     PISSN: 09209964     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.schres.2007.03.011     Document Type: Article

References (41)

1. Abi-Dargham A. Do we still believe in the dopamine hypothesis? New data bring new evidence. Int. J. Neuropsychopharmacol. 7 Suppl 1 (2004) S1-S5
2. Andreasen N.C. The Scale for the Assessment of Negative Symptoms (SANS): conceptual and theoretical foundations. Br. J. Psychiatry 7 (1989) 49-58 (Suppl. Nov.)
3. Annett M. A classification of hand preference by association analysis. Br. J. Psychol. 61 (1970) 303-321
4. Appelbaum P.S., and Grisso T. The MacArthur Competence Assessment Tool. Clin. Res. 1 (1996)
5. Arnsten A.F., and Li B.M. Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol. Psychiatry 57 (2004) 1377-1384
6. Arnsten A.F., Cai J.X., Murphy B.L., and Goldman-Rakic P.S. Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. Psychopharmacology (Berl) 116 (1994) 143-151
7. Barch D.M., Csernansky J., Conturo T., Snyder A.Z., and Ollinger J. Working and long-term memory deficits in schizophrenia. Is there a common underlying prefrontal mechanism?. J. Abnorm. Psychology 111 (2002) 478-494
8. Blanchet P.J., Fang J., Gillespie M., Sabounjian L., Locke K.W., Gammans R., Mouradian M.M., and Chase T.N. Effects of the full dopamine D1 receptor agonist dihydrexidine in Parkinson's disease. Clin. Neuropharmacol. 21 (1998) 339-343
9. Boyson S.J., Mcgonigle P., and Molinoff P.B. Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J. Neurosci. 6 (1986) 3177-3188
10. Brewster W.K., Nichols D.E., Riggs R.M., Mottola D.M., Lovenberg T.W., Lewis M.H., and Mailman R.B. Trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine: a highly potent selective dopamine D1 full agonist. J. Med. Chem. 33 (1990) 1756-1764
11. Carlsson A., and Lindqvist M. Effect of chlorpromazine or haloperidol on formation of 3methoxytyramine and normetanephrine in mouse brain. Acta Pharm. Toxicol. (Copenh) 20 (1963) 140-144
12. Castner S.A., Williams G.V., and Goldman-Rakic P.S. Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation. Science 287 (2000) 2020-2022
13. Creese I., Burt D.R., and Snyder S.H. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192 (1976) 481-483
14. Davis K.L., Kahn R.S., Ko G., and Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am. J. Psychiatry 148 (1991) 1474-1486
15. De Beaurepaire R., Labelle A., Naber D., Jones B.D., and Barnes T.R. An open trial of the D1 antagonist SCH 39166 in six cases of acute psychotic states. Psychopharmacology (Berl) 121 (1995) 323-327
16. Den Boer J.A., Van Megen H.J., Fleischhacker W.W., Louwerens J.W., Slaap B.R., Westenberg H.G., Burrows G.D., and Srivastava O.N. Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia. Psychopharmacology (Berl) 121 (1995) 317-322
17. Goldman-Rakic P.S. The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia. Biol. Psychiatry 46 (1999) 650-661
18. Goldman-Rakic P.S., Lidow M.S., and Gallager D.W. Overlap of dopaminergic, adrenergic, and serotoninergic receptors and complementarity of their subtypes in primate prefrontal cortex. J. Neurosci. 10 (1990) 2125-2138
19. Goldman-Rakic P.S., Castner S.A., Svensson T.H., Siever L.J., and Williams G.V. Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive function. Psychopharmacology 174 (2004) 3-16
20. Gonzalez-Islas C., and Hablitz J.J. Dopamine enhances EPSCs in layer II-III pyramidal neurons in rat prefrontal cortex. J. Neurosci. 23 (2003) 867-875
21. Green M. What are the functional consequences of neurocognitive deficits in schizophrenia?. Am. J. Psychiatry 153 (1996) 321-330
22. Karlsson P., Smith L., Farde L., Harnryd C., Sedvall G., and Wiesel F.A. Lack of apparent antipsychotic effect of the D1-dopamine receptor antagonist SCH39166 in acutely ill schizophrenic patients. Psychopharmacology (Berl) 121 (1995) 309-316
23. Lachowicz J.E., and Sibley D.R. Molecular characteristics of mammalian dopamine receptors. Pharmacol. Toxicol. 81 (1997) 105-113
24. Lidow M.S., and Goldman-Rakic P.S. A common action of clozapine, haloperidol, and remoxipride on D1- and D2-dopaminergic receptors in the primate cerebral cortex. Proc. Natl. Acad. Sci. U. S. A. 91 (1994) 4353-4356
25. Lidow M.S., Elsworth J.D., and Goldman-Rakic P.S. Down-regulation of the D1 and D5 dopamine receptors in the primate prefrontal cortex by chronic treatment with antipsychotic drugs. J. Pharmacol. Exp. Ther. 281 (1997) 597-603
26. Lovenberg T.W., Brewster W.K., Mottola D.M., Lee R.C., Riggs R.M., Nichols D.E., Lewis M.H., and Mailman R.B. Dihydrexidine, a novel selective high potency full dopamine D-1 receptor agonist. Eur. J. Pharmacol. 166 (1989) 111-113
27. Mailman R.B., Schulz D.W., Lewis M.H., Staples L., Rollema H., and Dehaven D.L. SCH-23390: a selective D1 dopamine antagonist with potent D2 behavioral actions. Eur. J. Pharmacol. 101 (1984) 159-160
28. Mailman R.B., Huang X., and Nichols D.E. Dopamine D1 full agonists and Parkinson's disease. Curr. Opin. Investig. Drugs (2001) 21582-21591
29. Michaelides M.R., Hong Y., Didomenico S.J., Asin K.E., Britton D.R., Lin C.W., Williams M., and Shiosaki K. (5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1-ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431). J. Med. Chem. 38 (1995) 3445-3447
30. Mottola D.M., Brewster W.K., Cook L.L., Nichols D.E., and Mailman R.B. Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist. J. Pharmacol. Exp. Ther. 262 (1992) 383-393
31. Mu, Q., Johnson, K., Morgan, P., Grenesko, E., Molnar, C., Anderson, B., Nahas, Z., Kozel, F.A., Kose, S., Knable, M., Fernandes, P., Nichols, D., Mailman, R., George, M.S., in press. A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal cortical perfusion in schizophrenia. Schizophr. Res.
32. Pennebaker J.W. The Psychology of Physical Symptoms (1982), Springer-Verlag, New York
33. Rascol O., Blin O., Thalamas C., Descombes S., Soubrouillard C., Azulay P., Fabre N., Viallet F., Lafnitzegger K., Wright S., Carter J.H., and Nutt J.G. ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease. Ann. Neurol. 45 (1999) 736-741
34. Salmi P., Isacson R., and Kull B. Dihydrexidine-the first full dopamine D1 receptor agonist. CNS Drug Rev. 10 (2004) 230-242
35. Sawaguchi T., and Goldman-Rakic P.S. D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science 251 (1991) 947-950
36. Schneider J.S., Sun Z.Q., and Roeltgen D.P. Effects of dopamine agonists on delayed response performance in chronic low-dose MPTP-treated monkeys. Pharmacol. Biochem. Behav. 48 (1994) 235-240
37. Schulz D.W., Stanford E.J., Wyrick S.W., and Mailman R.B. Binding of [3H]SCH23390 in rat brain: regional distribution and effects of assay conditions and GTP suggest interactions at a D1-like dopamine receptor. J. Neurochem. 45 (1985) 1601-1611
38. Seeman P., and Lee T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188 (1975) 1217-1219
39. Steele T.D., Hodges D.B., Levesque T.R., Locke K.W., and Sandage B.W. The D1 agonist dihydrexidine releases acetylcholine and improves cognition in rats. Ann. N. Y. Acad. Sci. 777 (1996) 427-430
40. Taylor J.R., Lawrence M.S., Redmond D.E.J., Elsworth J.D., Roth R.H., Nichols D.E., and Mailman R.B. Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys. Eur. J. Pharmacol. 199 (1991) 389-391
41. Watson D., Weber K., Assenheimer J.S., Clark L.A., Strauss M.E., and Mccormick R.A. Testing a tripartite model: I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales. J. Abnorm. Psychology 104 (1995) 3-14