[The effect of a new cholinolytic-[3H] tricyclopinate on human brain muscarinic receptors].
The binding characteristics of the novel cholinergic antagonist [3H] tricyclopinate with muscarinic receptors from human cerebral cortex were investigated in comparison with [3H] QNB by performing radioligand binding assays. As revealed by saturation experiments, the binding parameters of [3H] tricyclopinate (Kd = 0.044 nmol.L-1, Bmax = 514 fmol.mg-1) were almost identical with those of [3H]QNB (Kd = 0.040 nmol.L-1, Bmax = 508 fmol.mg-1). Both ligands fit a one site model of receptor-ligand interaction. Tricyclopinate showed a potency comparable to QNB on muscarinic receptors in inhibition experiments. However, some differences also existed between tricyclopinate and QNB. Kinetic experiments showed that both the association and dissociation of tricyclopinate (K1 = 1.40 (nmol.L-1)-1.min-1, K2 = 0.39 min-1) with muscarinic receptors were quicker than QNB (K1 = 0.65 (nmol.L-1)-1.min-1, K2 = 0.005 min-1). In addition, tricyclopinate behaved differently from QNB in the response of the dissociation profile to the allosteric modulation of gallamine. These results demonstrated that tricyclopinate has comparable affinity to muscarinic receptors with QNB but might interact with them in a different way. The introduction of [3H] tricyclopinate might complement the use of [3H] QNB in the study of central muscarinic receptors.
Yan
Z
Z
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850.
Hong
X Z
XZ
Liu
C G
CG
Ran
Y Z
YZ
D002540:Cerebral Cortex / Q000378:metabolism*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000187:drug effects*
D018680:Cholinergic Antagonists; D006575:Heterocyclic Compounds, 3-Ring; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C437004:tricyclopinate; D011813:Quinuclidinyl Benzilate