The buspirone challenge test clearly distinguishes ME/CFS patients from healthy controls: why is it not being developed and deployed?

[ScoutB]

While I'm at it, I've had this somewhat-relevant paper open in a tab for a while:
Occupancy of Dopamine D3 and D2 Receptors by Buspirone: A [11C]-(+)-PHNO PET Study in Humans

They gave people a radioligand that binds to dopamine receptors, as well as various doses of buspirone. Then they measured how buspirone competed with the radioligand for dopamine receptors.

(DRD2 = dopamine receptor D2, DRD3 = dopamine receptor D3)

[..] findings suggest [buspirone] has high in vitro affinity for dopamine receptor D3.

No study has explored the occupancy of DRD3 by buspirone in humans. Here, we used positron emission tomography (PET) and the D3-preferring probe, [11C]-(+)-PHNO, to test the hypothesis that buspirone will occupy (i.e. decrease [11C]-(+)-PHNO binding) the DRD3 more readily than the DRD2. Eight healthy participants underwent [11C]-(+)-PHNO scans after single oral dose administration of placebo and 30, 60, and 120 mg of buspirone in a single-blind within-subjects design.

Two of their results might be of interest for us.
(1) Prolactin release correlated to dopamine receptor occupancy by buspirone:

[11C]-(+)-PHNO binding in DRD2- and DRD3-rich areas was decreased by the highest (60–120 mg), but not the lowest (30 mg), doses of buspirone. The maximal occupancy obtained was ~25% in both areas. Plasma levels of prolactin (a DRD2 marker) correlated with percentage occupancy after orally administered buspirone.

(2) in vitro buspirone is much more selective for D3 than D2 (which is interesting because prolactin release is controlled by D2 receptors). However, this study found that in vivo the D2 vs D3 selectivity of buspirone seems to be more equally balanced:

The in vitro data indicate a twofold affinity and an 11-fold functional selectivity [of buspirone] for DRD3 over 5HT1A, and 70-fold affinity over DRD2 (Kula et al, 1994), with metabolites of buspirone also binding with higher affinity to DRD3 relative to DRD2 (Bergman et al, 2013).

Our data indicate for the first time that acute doses of buspirone can occupy DRD2 and DRD3 in human subjects. This occupancy was in the same range for the DRD2 vs DRD3 and the maximum occupancy achieved during acute single-dose regimen was modest with the doses of buspirone tested.

 

[hotblack]

Thanks @ScoutB that’s really useful.

DecodeME Locuszoom for DRD2 which I guess you could say maybe shows a little hump in the area but nothing significant. And not even a blip on DRD1, 3 or 4.