Low-dose prazosin in combination with 5-HT6 antagonist PRX-07034 has antipsychotic effects.
Can J Physiol Pharmacol
; 93(1): 13-21, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25429515
ABSTRACT
An extensive amount of research has focused on the development of new pharmacological agents to treat schizophrenia. Varying from person to person, schizophrenia is a heterogeneous disease with symptoms of positive, negative, and cognitive deficits. PRX-07034, a 5-hydroxytryptamine6 (5-HT6) receptor antagonist has been evaluated for its potential in treating obesity and cognitive deficits. This study evaluated PRX-07034 (0.1, 0.3, and 1.0 mg/kg body mass, by intraperitoneal (i.p.) injection), in combination with a low dose of prazosin (0.3 mg/kg, i.p.), for its antipsychotic potential. The research utilized a stereotypy assay, an open field test, an object recognition task, and prepulse inhibition. Dizocilpine, a non-competitive N-methyl-d-aspartate (NMDA) antagonist, was also administered in the above-mentioned assays as a psychomimetic. The combination of PRX-07034 and prazosin alleviated stereotypy and hyperlocomotor activity while enhancing memory in an object recognition task, and reversed sensory-gating deficits induced by dizocilpine. Examination of the medial prefrontal cortex revealed that a combination of PRX-07034 and prazosin reduced the dizocilpine-mediated increase of 5-HT. These results suggest that the combination of a 5-HT6 antagonist with low doses of prazosin could have therapeutic potential in the treatment of schizophrenia.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antagonistas da Serotonina
/
Antipsicóticos
/
Prazosina
/
Receptores de Serotonina
/
Antagonistas de Receptores Adrenérgicos alfa 1
Limite:
Animals
Idioma:
En
Revista:
Can J Physiol Pharmacol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Índia