Studies on histaminergic compounds, Part VII. Histamine H2-binding on guinea-pig cerebral cortex compared to histamine (ant)agonism.
The pKD values of series of H2-active compounds, obtained from displacement curves of 3H-tiotidine from a guinea-pig cerebral cortex homogenate were compared with the pA2/pD2 values of these compounds on the right atrium of the same animal species. A good correlation was found between the cortex pKD value and the pharmacological activity on the right atrium, especially with the antagonists, the partial agonists and the agonistic impromidine analogues (guanidines). The poor correlation between cortex pKD and atrium pD2 of some other agonists (the amines) might be explained by the presence of spare receptors for these compounds. The different number of spare receptors for the guanidines and the amines might be explained by the differences in base strength of these compounds.
Sterk
G J
GJ
Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Kramer
K
K
van der Goot
H
H
Timmerman
H
H
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D011869:Radioligand Assay; D011970:Receptors, Histamine H2 / Q000187:drug effects* / Q000378:metabolism
D006635:Histamine H2 Antagonists; D007093:Imidazoles; D011970:Receptors, Histamine H2; C065114:VUF 8414