Will Lumateperone have less dopamine blocking than other antipsychotics?
And do you think it will have less sexual side effects than other antipsychotics?
Apparently it does block less dopamine then current antipsychotics…
“This level of occupancy is lower than most other antipsychotic drugs at their efficacious doses and likely contributes to the favorable safety and tolerability profile of lumateperone with reduced risk for movement disorders and hyperprolactinemia.”
Lumateperone is still very new, and not enough research has been done on it in regards to sexual side effect profile.
APs like this one gives me hope for the future treatment of psychotic disorders.
Eventually, they will figure out how to pinpoint certain dopamine receptors and leave others untouched, so that sexual side effects won’t happen with new treatments in the future. Will this happen in our lifetime? I hope so.
This level of occupancy is lower “THAN MOST OTHER ANTIPSYCHOTICS” drugs at their efficacious doses and likely contributes to the favorable safety and tolerability profile of lumateperone with reduced risk for movement disorders and hyperprolactinemia.
They say “than most other antipsychotics” which other antipsychotic has less dopamine blocking than Lumateperone? From studies it shows Lumateperone Peak d2 blocking is at 39%
Clozapine is considered to be unusual in that it has a potent antipsychotic effect without exceeding 65% D2 ocupancy - it actually does exceed that but apparently only for a short time after dosing. Most other antipsychotics are around 65%-80% occupancy.
As far as I can tell, from what little is published.
In this study, using a 60mg dose (42mg is the dosage they have settled on for the trials) the occupancy peaked at 39% 1 hr post dose. Comparing that to one of the other ones that has fairly low D2 occupancy, quetiapine, it took 8 hours for that drug to get to 40% occupancy (it starts around 65%).
I’m not a doctor but this is what the Nature study said:
Mean peak dorsal striatal D2RO was 39% at 60 mg ITI-007 occurring 1 h post-dose. Lumateperone was well-tolerated with a favorable safety profile in this study. There were no clinically significant changes in vital signs, ECGs, or clinical chemistry laboratory values, including prolactin levels. There were no adverse event reports of akathisia or other extrapyramidal motor side effects; mean scores on motor function scales indicated no motor disturbances with lumateperone treatment. This level of occupancy is lower than most other antipsychotic drugs at their efficacious doses and likely contributes to the favorable safety and tolerability profile of lumateperone with reduced risk for movement disorders and hyperprolactinemia.
Reading down futher there is a chart that shows occupancy over a 24 hour period.It drops off to around 10% after 24 hours.
Quetiapine is sold as Seroquel - it is one that has lower D2 occupancy than many others, but it has a short half life so at 24 hours post dose there’s not much occupancy of D2 either. Quetiapine I would say starts higher (than lumateperone) but rapidly diminishes in its D2 blocking vs lumateperone til they both end up at very low levels prior to the next dose.
From two of the trials it seemed about on par with risperidone in terms of reduction in symptoms.
In the Nature paper on receptor occupancy there was one person who for whatever reason processed the medication differently and had a ~50% occupancy (vs 39%) and he had a greater reduction in symptoms. However that’s one guy. Also that level is considered to be under the threshold for the worst side effects of D2 blocking APs.
My guess is overall it’ll end up being about as effective as others, you’ll have some for whom it works great, some for whom it doesn’t work at all, and most of the people will be in the middle with partial relief. Probably the best thing about it is its possibly much better side effect and safety profile.