Compositions and methods related to serotonin 5-HT1A receptors

A method of diagnosing or 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, or a pharmaceutically acceptable salt thereof, 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, or a pharmaceutically acceptable salt thereof, 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 to *, and wherein the PET detectable label is 11C or 18F, and wherein Z is CH2F when 11C is present in R1 or *;
• 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.

A method for imaging the 5-HT1A receptor comprising:

• (i) administering a pharmaceutical composition comprising a compound having a structure according to Formula I to a mammal
• or a pharmaceutically acceptable salt thereof;
• wherein R1 is an optionally lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 is optionally 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
• 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, and wherein Z is CH2F when 11C is present in R1 or *;
• and
• (ii) performing a PET scan on said mammal.

A method of quantifying serotonin in vivo comprising:

• (i) administering a pharmaceutical composition comprising a compound having a structure according to Formula I, or a pharmaceutically acceptable salt thereof, to a mammal
• wherein R1 is an optionally lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 is optionally 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;
• and
• 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, and wherein Z is CH2F when 11C is present in R1 or *;
• (ii) performing a PET scan on said mammal;
• and
• (iii) correlating a PET signal quantity with a serotonin concentration.

A ligand-receptor complex comprising:

• (i) a compound having a structure according to Formula I
• wherein R1 is an optionally lower alkyl, alkoxy, halogen, or hydrogen, and wherein at least one carbon atom in R1 is optionally 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;
• and
• 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, and wherein Z is CH2F when 11C is present in R1 or *;
• and
• (ii) a 5-HT1A receptor.