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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Neuroleptic binding to muscarinic M2 receptors of normal human heart in vitro and comparison with binding to M1 and dopamine D2 receptors of brain.

We determined by radioligand binding the equilibrium dissociation constants (Kd's) for seventeen neuroleptics at muscarinic M2 receptors of human heart atrium and compared these data with our previous data for binding to muscarinic M1 and dopamine D2 receptors of human brain. At the M2 receptor, the most potent compound was thioridazine; the least, molindone. If selectivity is defined as Kd at one receptor less than or equal to 0.1 Kd at the other receptor, no compound was selective for the M2 subtype. Two compounds, clozapine and triflupromazine, were selective for the M1 subtype. Thus, few neuroleptics have the assumed preferred property of M1 over M2 subtype selectivity. Such a feature could reduce extrapyramidal side effects, while reducing the likelihood of certain cardiac side effects.[1]


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