THE BINDING OF [3H]MEPYRAMINE TO HISTAMINE H1 RECEPTORS IN GUINEA-PIG BRAIN

The promethazine-sensitive binding of ³H]mepyramine to a membrane fraction from guinea-pig whole brain is saturable with a dissociation constant of 1.7 × 10^-9M. The maximum amount of ³H]mepyramine binding varied widely between preparations, range 122–365 pmol/g protein, with a mean value of 227 ± 52 pmol/g protein. The inhibition of ³H]mepyramine binding by a number of drugs correlated closely with their potency as histamine H₁ antagonists. (+) Chlorpheniramine was 240-fold more potent as an inhibitor of ³H]mepyramine binding than (-)-chlorpheniramine. All antagonists inhibited the binding of ³H]mepyramine to the same extent, but the Hill coefficients characterising the inhibition curves did not all approximate to unity, the value expected for a simple antagonist-receptor equilibrium. The distribution of histamine H₁ receptors, defined by the promethazine-sensitive binding of ³H]mepyramine, in 11 different brain regions was uneven with the largest amounts in cerebellum, superior and inferior colliculus and hypothalamus and the smallest in caudate nucleus, brain stem and spinal cord.