Differentiation of muscarinic cholinergic receptor subtypes in human cortex and pons: implications for anti-motion sickness therapy.
Radioligand binding studies were used to analyze muscarinic cholinergic receptor subtypes in human cortex and pons. Muscarinic cholinergic receptors were labeled by 3H-quinuclidinyl benzilate (3H-QNB). Scopolamine was equipotent in both brain regions and did not discriminate subtypes of 3H-QNB binding. By contrast, the M1 selective antagonist pirenzepine was approximately 33-fold more potent in human cortex than pons. Carbachol, a putative M2 selective agonist, was more than 100-fold more potent in human pons than cortex. These results demonstrate that the human pons contains a relatively large proportion of carbachol sensitive muscarinic cholinergic receptors. Drugs targeted to this subpopulation of muscarinic cholinergic receptors may prove to be effective anti-motion sickness agents with less side effects than scopolamine.
McCarthy
B G
BG
Department of Neurology, Stanford University Medical Center, CA 94305.
Peroutka
S J
SJ
D002217:Carbachol / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D006801:Humans; D009041:Motion Sickness / Q000628:therapy*; D010890:Pirenzepine / Q000378:metabolism; D011149:Pons / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012601:Scopolamine / Q000378:metabolism
D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D012601:Scopolamine