Abstract

The novel benzamide derivative YM 43611 is a selective dopamine D3/D4 receptor antagonist with an in vitro profile of effects suggestive of atypical antipsychotic activity. In this study the effects of YM 43611 were compared with those of the conventional antipsychotic haloperidol and the atypical antipsychotic clozapine in behavioral studies with squirrel monkeys. Like haloperidol and clozapine, YM 43611 induced dose-related decreases in response rate under a fixed-interval schedule of stimulus-shock termination. Like halopeidol, but unlike clozapine, YM 43611 also antagonized the behavioral effects of (+)amphetamine in a surmountable manner and induced dose-related increases in static and unusual postures indicative of catalepsy. Both YM 43611 and haloperidol failed to substitute for clozapine in monkeys trained to discriminate clozapine from vehicle. Although YM 43611 appears to have in vitro effects predictive of atypical antipsychotic activity, its in vivo effects in primates were qualitatively similar to those of the conventional antipsychotic haloperidol.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-35
Application #
3718969
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
35
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:
Ma, Qi; Ruan, Hongyu; Peng, Lisheng et al. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A 114:E8760-E8769
Shang, L; Duan, L; Perkey, K E et al. (2017) Epithelium-innate immune cell axis in mucosal responses to SIV. Mucosal Immunol 10:508-519

Showing the most recent 10 out of 365 publications