D1
9-16-2021 links: Dopamine GPCR reference:
D1 #
Gs-coupled. Also consists of D5.
-
Apparently eye blink rate is a measure of D1 activity.
-
Promotes release of Acetylcholine as they work together for eliciting focus.
-
Antagonism treats tourette’s and the euphoric effects of cocaine.
-
Mechanisms for the Modulation of Dopamine D1 Receptor Signaling in Striatal Neurons
- D1-Adenosine A1 heteromer: decrease in D1 affinity.
- D1-D3: increasein D1 affinity and stabilizing of D1 at membrane.
- D1-NMDAR heteromer: anchors D1 at spines.
- Part of dendritogenesis/axon guidance maybe?
- Tuning the engine of cognition: A focus on NMDA/D1 receptor interactions in prefrontal cortex Picard cited this regarding it as IQ-dependent networks
-
PAM #
- Mutual Cooperativity of Three Allosteric Sites on the Dopamine D1 Receptor
- I don’t think there’s a U-shaped response curve for PAMs.
-
Impaired β-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 dopamine receptor
- They exhibit distinct binding to the D1R orthosteric site and a novel functional profile including minimal receptor desensitization, reduced recruitment of β-arrestin, and sustained in vivo efficacy.
-
Identification of Positive Allosteric Modulators of the D 1 Dopamine Receptor That Act at Diverse Binding Sites
- Tested 500,000 compounds and identified a single dopamine D1 positive allosteric modulator (D1R PAM), and this lead compound was used to generate 4 drug candidates.
- Sirsadalot’s critique is arrestin, dynorphin, and malfunctioning synaptogenesis because D2 will bind at the same time as D1 and create behavioral sensitization, and it probably will downregulate regardless, and especially considering the production of dopamine thereafter