Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites.
Article Details
- CitationCopy to clipboard
Hals PA, Hall H, Dahl SG
Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites.
Life Sci. 1988;43(5):405-12.
- PubMed ID
- 2899826 [ View in PubMed]
- Abstract
In vitro binding affinities of chlorpromazine, fluphenazine, levomepromazine, perphenazine and some of their metabolites for dopamine D2 receptors, alpha 1- and alpha 2 adrenoceptors in rat brain were previously reported from our laboratories. The present study reports the in vitro binding affinities of the same compounds for muscarinic cholinergic receptors and for histamine H1 receptors in rat brain, using 3H-quinuclidinyl benzilate and 3H-mepyramine as radioligands. Chlorpromazine, levomepromazine, and their metabolites had 5-30 times higher binding affinities for muscarinic cholinergic receptors than fluphenazine, perphenazine and their metabolites. Levomepromazine was the most potent and fluphenazine the least potent of the four drugs in histamine H1 receptor binding. 7-Hydroxy levomepromazine, 3-hydroxy levomepromazine and 7-hydroxy fluphenazine had only 10% of the potency of the parent drug in histamine H1 receptor binding, while the 7-hydroxy-metabolites of chlorpromazine and perphenazine had about 75% of the potency of the parent drug in this binding system. Their histamine H1 receptor binding affinities indicate that metabolites may contribute to the sedative effects of chlorpromazine and levomepromazine.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Chlorpromazine Histamine H1 receptor Protein Humans YesAntagonistDetails Methotrimeprazine Histamine H1 receptor Protein Humans UnknownAntagonistDetails Methotrimeprazine Muscarinic acetylcholine receptor M1 Protein Humans UnknownAntagonistDetails Methotrimeprazine Muscarinic acetylcholine receptor M2 Protein Humans UnknownAntagonistDetails Methotrimeprazine Muscarinic acetylcholine receptor M3 Protein Humans UnknownAntagonistDetails Methotrimeprazine Muscarinic acetylcholine receptor M4 Protein Humans UnknownAntagonistDetails Methotrimeprazine Muscarinic acetylcholine receptor M5 Protein Humans UnknownAntagonistDetails Promazine Histamine H1 receptor Protein Humans UnknownAntagonistDetails