Medicinal Chemistry

NEUROTRANSMITTERS AND THEIR RECEPTORS 263

the blood–brain barrier, central receptors can use only the locally synthesized

histamine. Occupation of the H 1 receptor by an agonist does not activate adenylate

cyclase (AC); it appears to use phosphoinositol as second messenger. H 1 receptors

are not very specific and are occupied by antidepressants and neuroleptics as well.

This explains the sedative effect of all three classes of drugs. The H 1 receptors are

easily solubilized and have been purified on lectin affinity columns, indicating their

glycoprotein nature.

Figure 4.11Histamine metabolism.