Neuropharmacological profiles of a novel atypical antipsychotic, NRA0562, in rats.
Neuropharmacological profiles of 5-(2-[4-(6-fluoro-1H-indole-3-yl) piperidine-1-yl] ethyl)-4-(4-fluorophenyl) thiazole-2-carboxylic acid amide (NRA0562) in rats were examined using electrophysiological and immunohistochemical methods. The firing rates of the substantia nigra pars compacta (A9) and the ventral tegmental area (A10) dopamine neurons were inhibited by methamphetamine (1 mg/kg, i.v.). NRA0562 dose-dependently reversed the inhibitory effects of methamphetamine on A9 and on A10 dopamine neurons. NRA0562 was more potent to reverse the inhibitory effects of methamphetamine on A10 (ED(50)=0.3 mg/kg) than on A9 (ED(50)=0.9 mg/kg) dopamine neurons. NRA0562 produced significant increases in Fos-like immunoreactivity in both the nucleus accumbens and the dorsolateral striatum. The difference between the number of Fos-like immunoreactivity produced by NRA0562 in the nucleus accumbens vs. dorsolateral striatum, referred to as the atypical index, was positive. Similar results could be observed with risperidone, an atypical antipsychotic. These results suggest that NRA0562 may have the atypical antipsychotic activities seen with risperidone, but without the liability of motor side effects typical of classical antipsychotics.
Kawashima
N
N
CNS Diseases Research, Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Saitama, Saitama 330-8530, Japan. s16386@ccm.taisho.co.jp
Funakoshi
T
T
Omura
T
T
Chaki
S
S
Kameo
K
K
Okuyama
S
S
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
C433508:5-(2-(4-(6-fluoro-1H-indole-3-yl)piperidine-1-yl)ethyl)-4-(4-fluorophenyl)thiazole-2-carboxylic acid amide; D014150:Antipsychotic Agents; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D013844:Thiazoles; D008694:Methamphetamine; D018967:Risperidone; D004298:Dopamine