Compositions and methods related to serotonin 5-HT1A receptors
AssigneeThe Regents of the University of California
InventorsJogeshwar Mukherjee, Neil Saigal
Life of this patent
Estimating the term…
Abstract
Contemplated substituted arylpiperazinyl compounds, and most preferably 18F-Mefway, exhibit desirable in vitro and in vivo binding characteristics to the 5-HT1A receptor. Among other advantageous parameters, contemplated compounds retain high binding affinity, display optimal lipophilicity, and are radiolabeled efficiently with 18F-fluorine in a single step. Still further, contemplated compounds exhibit high target to non-target ratios in receptor-rich regions both in vitro and in vivo, and selected compounds can be effectively and sensitively displaced by serotonin, thus providing a quantitative tool for measuring 5-HT1A receptors and serotonin concentration changes in the living brain.
Claims12
A compound having a structure according to Formula I
- wherein R1 is OCH3 or O11CH3;
- X is N, and W is CH;
- Y is O, and wherein * denotes an optional 11C isotope;
- Q is optionally substituted cycloalkyl or cycloalkenyl;
- and
- wherein Z is lower alkyl;
- and
- wherein 11C is present in at least one of R1 and *.
A method of treating a panic disorder, a bipolar disorder, or a seizure disorder, comprising a step of administering a pharmaceutical composition that includes a compound having a structure according to Formula I to a mammal,
- wherein R1 is an optionally substituted lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 may be 11C;
- X and W are independently N or CH;
- Y is O, NR1, or S, and wherein * denotes an optional 11C isotope;
- Q is optionally substituted cycloalkyl or cycloalkenyl;
- and
- wherein Z is lower alkyl, and wherein a PET detectable label is covalently bound to Z when 11C is absent in R1 and *, and wherein the PET detectable label is 11C or 18F.
A method of quantifying serotonin in a neural tissue comprising:
- a step of administering a pharmaceutical composition comprising a compound having a structure according to Formula I to a mammal,
- wherein R1 is an optionally substituted lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 may be 11C;
- X and W are independently N or CH;
- Y is O, NR1, or S, and wherein * denotes an optional 11C isotope;
- Q is optionally substituted cycloalkyl or cycloalkenyl;
- and
- wherein Z is lower alkyl, and wherein a PET detectable label is covalently bound to Z when 11C is absent in R1 and *, and wherein the PET detectable label is 11C or 18F
- a step of performing a PET scan on the tissue, and
- a step of correlating a PET signal quantity with a serotonin concentration in the tissue.
Dependencies are inferred from the claim text.