We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

The Effects of a Selective D4 Dopamine Receptor Antagonist (L-745,870) in Acutely Psychotic Inpatients With Schizophrenia

Mark S. Kramer, MD, PhD; Barbara Last; Albert Getson, PhD; Scott A. Reines, MD, PhD
Arch Gen Psychiatry. 1997;54(6):567-572. doi:10.1001/archpsyc.1997.01830180085011.
Text Size: A A A
Published online

Background:  Based mainly on the selective antagonism of clozapine at D4 compared with D2 dopamine receptors, hopes have run high that a selective D4 dopamine receptor antagonist might improve the pharmacological treatment of patients with schizophrenia. We report, to our knowledge, the first multicenter study of the antipsychotic potential of a highly specific D4 dopamine receptor antagonist (ie, L-745,870) in patients with acute schizophrenia.

Methods:  Thirty-eight acutely psychotic and neuroleptic responsive (by history) newly admitted inpatients with schizophrenia were randomized to 4 weeks of doubleblind treatment (2:1) with either L-745,870 (n=26), 15 mg/d, or placebo (n=12) after a 3- to 5-day placebo run-in period.

Results:  Overall, a greater percentage of patients receiving L-745,870 compared with patients receiving placebo discontinued the study for insufficient therapeutic response (32% vs 16%). At the end of 4 weeks by last observation carried forward analysis, the mean change from baseline to week 4 on the total Brief Psychiatric Rating Scale favored placebo (ie,—8 points [—15% change from baseline] vs—1 point [—2% change from baseline] for placebo vs L-745,870, P=.09). Similar differences in favor of placebo in changes from baseline mean scores were observed for the not carried forward analysis on the total Brief Psychiatric Rating Scale (P<.03), for not carried forward and last observation carried forward analyses on the sum of selected positive symptom items of the Brief Psychiatric Rating Scale, and for the Clinical Global Impression analysis (P=.03, last observation carried forward). A greater percentage of patients receiving L-745,870 had scores indicative of some level of worsening (compared with baseline) on the total Brief Psychiatric Rating Scale and the Clinical Global Impressions' Severity of Illness Scale as well as positive symptoms compared with those receiving placebo.

Conclusion:  The selective D4 dopamine receptor antagonist L-745,870 was ineffective as an antipsychotic for the treatment of neuroleptic responsive inpatients with acute schizophrenia.


Sign in

Purchase Options

• Buy this article
• Subscribe to the journal





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.