Specific Binding of [³H]Pyrilamine to Histamine H₁ Receptors in Guinea Pig Brain In Vivo: Determination of Binding Parameters by a Kinetic Four‐Compartment Model

The binding of [³H]pyrilamine, a selective ligand of histamine H₁ receptors, to guinea pig brain in vivo was compared with its binding to a brain homogenate. The pharmacological properties (regional distribution, saturability, and stereoselectivity) of the [³H]pyrilamine binding in vivo were similar to those of the in vitro binding to brain homogenate. A dynamic four‐compartment model was proposed for the analysis of the kinetics of [³H]pyrilamine binding in vivo. The receptor constants in vivo were determined by a computer‐fitting method after correcting the radioactivity of arterial plasma and brain for the presence of radioactive metabolites. The in vivo association and dissociation were 213 and 42 times, respectively, slower than those of in vitro binding at 37°C. A possible mechanism for slow association and dissociation in vivo is discussed.