Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine

S. L. Dewey, R. R. Macgregor, J. D. Brodie, B. Bendriem, P. T. King, N. D. Volkow, D. J. Schlyer, J. S. Fowler, A. P. Wolf, S. J. Gatley, Robert Hitzemann

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The muscarinic cholinergic system has been mapped in vivo in human and baboon brain using [N-11C-methyl]-benztropine and high resolution positron emission tomography (PET). [N-11C-methyl]-benztropine uptake was observed in frontal, parietal, occipital, and temporal cortices as well as in subcortical structures including the corpus striatum and thalamus. Uptake continued to increase in baboon and human brain in all areas over an 80 minute experimental period with the exception of the cerebellum where the accumulation of radioactivity began to decrease by 25 minutes postinjection. The ratio of incorporation of [N-11C-methyl]-benztropine between corpus striatum/cerebellum was 1.53 and 1.46 in humans and baboons, respectively, at 60 minutes. Blocking studies in baboons using the muscarinic cholinergic antagonists scopolamine and benztropine and the muscarinic cholinergic agonist pilocarpine combined with blocking studies in humans using benztropine indicate that the binding of this compound is specific for the muscarinic cholinergic system. Pretreatment with the potent dopamine reuptake blocker nomifensine produced no effect on the incorporation of radioactivity in any baboon brain region examined. Analysis of labelled plasma metabolites indicates that in humans, the rate of metabolism of [N-11C-methyl]-benztropine is slow (83.0% unchanged at 30 minutes postinjection) differing quite dramatically from the rate of metabolism observed in baboons (43.4% unchanged at 30 minutes postinjection). These data combined with postmortem studies in humans and primates demonstrate that [N-11C-methyl]-benztropine is a suitable muscarinic cholinergic ligand for use in humans and baboons with PET.

Original languageEnglish (US)
Pages (from-to)213-223
Number of pages11
JournalSynapse
Volume5
Issue number3
DOIs
StatePublished - 1990
Externally publishedYes

Fingerprint

Benztropine
Papio
Muscarinic Receptors
Cholinergic Agents
Brain
Corpus Striatum
Positron-Emission Tomography
Cerebellum
Radioactivity
Nomifensine
Muscarinic Agonists
Occipital Lobe
Parietal Lobe
Pilocarpine
Muscarinic Antagonists
Scopolamine Hydrobromide
Dopamine Antagonists
Frontal Lobe
Temporal Lobe
Thalamus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Dewey, S. L., Macgregor, R. R., Brodie, J. D., Bendriem, B., King, P. T., Volkow, N. D., ... Hitzemann, R. (1990). Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine. Synapse, 5(3), 213-223. https://doi.org/10.1002/syn.890050307

Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine. / Dewey, S. L.; Macgregor, R. R.; Brodie, J. D.; Bendriem, B.; King, P. T.; Volkow, N. D.; Schlyer, D. J.; Fowler, J. S.; Wolf, A. P.; Gatley, S. J.; Hitzemann, Robert.

In: Synapse, Vol. 5, No. 3, 1990, p. 213-223.

Research output: Contribution to journalArticle

Dewey, SL, Macgregor, RR, Brodie, JD, Bendriem, B, King, PT, Volkow, ND, Schlyer, DJ, Fowler, JS, Wolf, AP, Gatley, SJ & Hitzemann, R 1990, 'Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine', Synapse, vol. 5, no. 3, pp. 213-223. https://doi.org/10.1002/syn.890050307
Dewey SL, Macgregor RR, Brodie JD, Bendriem B, King PT, Volkow ND et al. Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine. Synapse. 1990;5(3):213-223. https://doi.org/10.1002/syn.890050307
Dewey, S. L. ; Macgregor, R. R. ; Brodie, J. D. ; Bendriem, B. ; King, P. T. ; Volkow, N. D. ; Schlyer, D. J. ; Fowler, J. S. ; Wolf, A. P. ; Gatley, S. J. ; Hitzemann, Robert. / Mapping muscarinic receptors in human and baboon brain using [N-11C-methyl]-benztropine. In: Synapse. 1990 ; Vol. 5, No. 3. pp. 213-223.
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