{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:29:56Z","timestamp":1790375396629,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,7,30]],"date-time":"2003-07-30T00:00:00Z","timestamp":1059523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>[<jats:sup>18<\/jats:sup>F][3\u2010(3\u2010(3\u2010Fluoropropyl)thio)\u20101,2,5\u2010thiadiazol\u20104\u2010yl]\u20101,2,5,6\u2010tetrahydro\u20101\u2010methylpyridine ([<jats:sup>18<\/jats:sup>F]FP\u2010TZTP) is an M2 selective muscarinic agonist that may allow noninvasive studies of Alzheimer's disease with PET. 3\u2010(3\u2010(Propylthio)\u20101,2,5\u2010thiadiazol\u20104\u2010yl)\u20101,2,5,6\u2010tetrahydro\u20101\u2010methylpyridine (P\u2010TZTP), a nonfluorinated analog of FP\u2010TZTP, and unlabeled FP\u2010TZTP inhibited [<jats:sup>18<\/jats:sup>F]FP\u2010TZTP binding in vivo. Because muscarinic action of the loading dose of P\u2010TZTP administered might have had pharmacological effects, the apparent inhibition might have resulted from reduced delivery rather than competition with receptor\u2010binding. Therefore, we examined the effects of P\u2010TZTP or FP\u2010TZTP administration on cerebral blood flow (CBF) measured by the [<jats:sup>14<\/jats:sup>C]iodoantipyrine method and laser\u2010Doppler flowmetry in rats. Statistically significant synchronous decreases in both CBF and mean arterial blood pressure (MABP) were observed within the first minute following administration. The decreases in both CBF and MABP were prevented by pretreatment with atropine methyl bromide (M\u2010At), a peripheral muscarinic antagonist, and coadministration of M\u2010At with either FP\u2010TZTP or P\u2010TZTP resulted in the same degree of inhibition of cerebral [<jats:sup>18<\/jats:sup>F]FP\u2010TZTP\u2010uptake 30 min after administration as observed without M\u2010At. Also, with programmed infusions designed to produce constant arterial concentrations of [<jats:sup>18<\/jats:sup>F]FP\u2010TZTP and FP\u2010TZTP, which avoid changes in CBF, significant inhibition of [<jats:sup>18<\/jats:sup>F]FP\u2010TZTP\u2010binding by FP\u2010TZTP was observed. These results indicate that inhibition of [<jats:sup>18<\/jats:sup>F]FP\u2010TZTP\u2010binding in the brain by P\u2010TZTP or FP\u2010TZTP in vivo occurs independently of their effects on CBF. The methods employed here may also be of interest to evaluate physiological effects of blocking agents utilized to validate other radiopharmaceuticals. Synapse 50:151\u2013163, 2003. Published 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.10257","type":"journal-article","created":{"date-parts":[[2003,8,12]],"date-time":"2003-08-12T15:26:50Z","timestamp":1060702010000},"page":"151-163","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of [<sup>18<\/sup>F]FP\u2010TZTP binding by loading doses of muscarinic agonists P\u2010TZTP or FP\u2010TZTP in vivo is not due to agonist\u2010induced reduction in cerebral blood 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