title: Low-dose prazosin in combination with 5-HT6 antagonist PRX-07034 has antipsychotic effects.
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.
authors.affiliation: a Discovery Research, Suven Life Sciences, Ltd., Serene Chambers, Road No. 5, Avenue 7, Banjara Hills, Hyderabad 500 055, India.
authors.forename: Renny
authors.initials: R
authors.lastname: Abraham
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Nirogi
authors.forename: Anil
authors.initials: A
authors.lastname: Shinde
authors.forename: Shantaveer
authors.initials: S
authors.lastname: Irupannanavar
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D011224:Prazosin / Q000008:administration & dosage*; D065808:Prepulse Inhibition / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000008:administration & dosage*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor; D011224:Prazosin
keywords: champ ouvert; inhibition de la réaction de sursaut; mesure de la stéréotypie; object recognition task; open field; prepulse inhibition; schizophrenia; schizophrénie; stereotypy assay; tâche de reconnaissance d’un objet