Pindolol binding to 5-HT1A receptors in the human brain confirmed with positron emission tomography.
The augmentation effect of (-)pindolol as used in combination with SSRI to treat major depression has been ascribed to blocking of dorsal raphe nucleus cell body 5-HT autoreceptors. In this study, the radioligand [carbonyl-11C]WAY-100635 and positron emission tomography were used to establish whether pindolol at a clinical dose level (10 mg s.o.d.) occupies 5-HT1A receptors in the human brain in vivo. Three healthy males were recruited and each subject was used as his own control. The 5-HT1A receptor occupancy was calculated for the frontal and temporal cortex and the raphe nuclei, using and a ratio analysis with the cerebellar cortex as the reference region. Maximal pindolol plasma concentration was reached within 3 h after drug administration. Two hours after pindolol administration, the regional 5-HT1A receptor occupancy was within the range 7-21% in the three subjects. The study confirms that the 5-HT1A-receptor may be a clinically significant target for pindolol.
Andrée
B
B
Karolinska Institutet, Department of clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. bengt.andree@neuro.ks.se
Thorberg
S O
SO
Halldin
C
C
Farde
L
L
D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D006801:Humans; D008297:Male; D010869:Pindolol / Q000493:pharmacokinetics / Q000494:pharmacology*; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D010869:Pindolol