Muscarinic subtype selectivity of tetrahydroaminoacridine: possible relationship to its capricious efficacy.
Tetrahydroaminoacridine discriminated slightly in its potency to displace [3H]N-methylscopolamine ([3H]NMS) binding from different muscarinic receptor subtypes (M2 greater than M1 greater than M3) and to allosterically decelerate ligand binding (M2 greater than or equal to M1 greater than M3). The steep displacement curves suggest that marked changes in receptor occupancy may occur within a relatively narrow dose range. Thus, individual inter-patient variability and inconsistent results in clinical studies may be related to blockade of muscarinic receptors, which would oppose the beneficial effects resulting from acetylcholinesterase inhibition.
Kiefer-Day
J S
JS
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore 21201.
Campbell
H E
HE
Towles
J
J
el-Fakahany
E E
EE
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D016466:CHO Cells / Q000187:drug effects; D006224:Cricetinae; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000235:genetics; D013619:Tacrine / Q000494:pharmacology*
D008024:Ligands; D011976:Receptors, Muscarinic; D013619:Tacrine