Xenomeline - Trospium
This is the neurotransmitter directly targeted by Xenomeline.
What is Acetylcholine?
This is a novel/unique Dopamine receptor activity of Lumateparone compared to other antipsychotics.
What is pre-synaptic D2 partial agonism?
This is the Dopamine receptor with highest binding affinity by Cariprazine.
What is the D3 receptor?
Akisthisia
What is Cariprazine (Vraylar)?
This is the dopaminergic pathway where Xenomeline has its selective anti-psychotic effects.
What is the meso-limbic pathway?
This is theorized reason dose titration is not necessary with Lumateparone.
What is pre-synaptic D2 partial agonism prevents the natural compensatory increase in DA caused by chronic post-synaptic D2 blockade
Compared to Aripiprazole, the degree of D2 partial antagonism vs partial-agonism is.
What is - Cariprazine has more D2 antagonism compared to Abilify while is still being a partial-agonist.
Urinary retention
What is Xenomeline/Trospium (Cobenfy)?
This is overall secondary end result (down-stream effect) of Xenomline's binding muscarinic cholinergic receptors.
What is inhibiting Dopamine release from the Ventral-tegmental Area (VTA) in the Meso-limbic pathway?
This is another neurotransmitter modulated by Lumateparone that is unique compared with other antipsychotics.
What is modulation of glutamate?
Cariprazine is metabolized by this P450 enzyme
What is CYP 3A4?
Sedation
What is Lumateperone (Caplyta)
These are three other dopaminergic pathways that Xenomeline does not effect, avoiding these commonly associated side effects from D2 blockade.
What are avoiding the:
1) Meso-cortical pathway - avoiding cognitive side effects
2 Nigro-striatal pathway - avoiding EPS/Parkinsonism side effects
3) Tubero-infundibular - avoiding hyperprolactinemia side effects
This is the enzyme responsible for primary metabolism of Lumateparone.
What is Cytochrome P450 3A4?
Excessive hedonistic behaviors (eg compulsive gambling)
What is Cariprazine (Vraylar)?
These are the two cholinergic receptors bound by Xenomeline, their location within the synapse (pre vs post synaptic), and their cross-regulatory effect(s) which inhibit Dopamine.
What are the
1) M1 receptor: presynaptic, activates GABA interneurons that inhibit Glutamate, thereby inhibiting DA release
2) M4 auto-receptor: presynaptic, down regulates cholinergic innervation of the VTA in M-L pathway, inhibiting DA release
This is the percent of post-synaptic D2 receptor occupancy from Lumateparone and the theorized advantage of this degree of receptor affinity compared to other antipsychotics.
What is only 28 - 30% post-synaptic D2 receptor occupancy, with the advantage of avoiding/minimizing risk of EPS (typically occurs at > 80% D2 receptor occupancy)
Serotonin Syndrome
What is Lumateperone (Caplyta)