[³H]clonidine binds at multiple high affinity states in human prefrontal cortex

[³H]Clonidine binds at particulate membrane fractions of human prefrontal cortex in a process that demonstrates high affinity, saturability, reversebility, α₂-adrenergic selectivity and the existence of multiple affinity states. At 37°C maximal specific [³H]clonidine binding was briefly attained at 10 and lasted only until 15 min, while at 21°C maximal binding was maintained from 20 to 90 min. At 21°C, rate dissociation studies and saturation analyses were at least biphasic, and adrenergic competitors decreased [³H]clonidine binding with Hill coefficients <0.70. Analysis of these data showed at least two affinity states with apparent K_Ds of 0.34 and 6.0 nM, and the order in which ligands decreased [³H]clonidine binding was clonidine > (-)-epinephrine > (-) > yohimbine > (+)-norepinephrine > (±) -isoproterenol > prazosin > serotonin.