title: Effects of the 5-HT1A receptor agonists buspirone and 8-OH-DPAT on pupil size in common marmosets.
abstract: As pupil size is affected by psychotropic drugs in all mammals, it has been used as a well-established clinical indicator for the preclinical and clinical development of novel drugs. It has been reported that activation of the serotonin (5-HT)1A receptor differently affects pupil response in rodents (mydriasis) and humans (miosis). Thus, it is important to establish a quantitative system for measuring pupil size using other species, such as nonhuman primates. Common marmosets have recently attracted a great deal of attention as suitable experimental animals in the psychoneurological field because of handling ease compared with other nonhuman primates and the requirement for small amounts of test drugs. In this study, we constructed a system for measuring changes in pupil size using an infrared eye-tracking camera and evaluated the effects on pupil size of the 5-HT1A receptor agonists buspirone, 8-OH-DPAT and buspirone active metabolite 1-(2-pyrimidinyl) piperazine. Our results show that both buspirone and 8-OH-DPAT significantly decrease pupil size in a dose-dependent manner. The 5-HT1A receptor antagonist WAY 100635 completely blocked both buspirone and 8-OH-DPAT-induced miosis, whereas 1-(2-pyrimidinyl) piperazine had no effect on pupil size. These results suggest that measurement of pupil size may be a useful biomarker for predicting the pharmacodynamics of new 5-HT1A receptor agonists.
authors.affiliation: aHigher Brain Function Research bBiomarker Group, Drug Development Research Laboratories cDMPK Group I, Preclinical Research Laboratories, Drug Research Division, Sumitomo Dainippon Pharma Co Ltd., Osaka, Japan.
authors.forename: Manato
authors.initials: M
authors.lastname: Kotani
authors.forename: Naoko
authors.initials: N
authors.lastname: Urushino
authors.forename: Itaru
authors.initials: I
authors.lastname: Natsutani
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002065:Buspirone / Q000008:administration & dosage / Q000494:pharmacology*; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D005260:Female; D007259:Infrared Rays; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone