Tandospirone stimulates prolactin secretion in the rat by an action at serotonin-1A receptors.
Tandospirone is an azapirone drug that has high affinity for serotonin-1A (5-HT-1A) receptors and preclinical effects predictive of antidepressant and/or anxiolytic efficacy. 5-HT-1A receptor agonists, such as 8-hydroxy-2-(di-n-propyl-amino)tetralin, increase the plasma prolactin concentration in rats, probably by an action in the brain that leads to an increase in prolactin release from the pituitary gland. The purpose of this study was to examine the effect of tandospirone on plasma prolactin concentration in awake, freely moving male rats. We found that i.v. administration of tandospirone results in a rapid and dose-related increase in the plasma prolactin concentration. The plasma prolactin level peaks about 10 min after injection and returns to base-line values within 30 min after injection. The ED50 of tandospirone to increase plasma prolactin levels is approximately 0.3 mg/kg. This effect of tandospirone is blocked by pretreatment with the 5-HT antagonists metergoline and NAN-190 and shows cross-desensitization with the 5-HT-1A agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin. Thus the effect of tandospirone on plasma prolactin concentration appears to be mediated by 5-HT-1A receptors. In contrast to this effect of tandospirone, 1-(2-pyrimidyl)-piperazine (1-PP), the common metabolite of tandospirone and other azapirone drugs, has no effect on plasma prolactin levels. The effect of chronic administration of tandospirone was examined by measuring the prolactin response to an acute i.v. injection of tandospirone 24 hr after the last of chronic injections of tandospirone (10 mg/kg, s.c., twice a day for 2 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)
Mulroney
S E
SE
Department of Physiology & Biophysics, Georgetown University School of Medicine, Washington, D.C.
Skudlarek
C
C
Shemer
A
A
Lumpkin
M D
MD
Kellar
K J
KJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002065:Buspirone / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D054833:Isoindoles; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D008711:Metergoline; C055267:tandospirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011388:Prolactin; C037921:1-(2-pyrimidinyl)piperazine; D002065:Buspirone