PSEMs

Pharmacologically Selective Effector Molecules (PSEMs) are inert ligands, specific for genetically-modified, chimeric ion channels, termed Pharmacologically Selective Actuator Modules (PSAMs). PSAMs containing the 5-HT3 ion pore domain allow activation of neuronal activity, while GlyR and GABAc containing chimeras are inhibitory

Products
Background
Literature

Agonists

Cat No Product Name / Activity
6425 PSEM 308 hydrochloride
PSAML141F-GlyR and PSAML141F,Y115F-5-HT3 chimeric ion channel agonist
6426 PSEM 89S
PSAML141F-GlyR and PSAML141F,Y115F-5-HT3 chimeric ion channel agonist
6865 uPSEM 792 hydrochloride
Highly potent PSAM4-GlyR and PSAM4-5-HT3 chimeric ion channel agonist; brain-penetrant
6866 uPSEM 817 tartrate
Highly potent and selective uPSAM4-GlyR and PSAM4-5-HT3 chimeric ion channel agonist; brain-penetrant

Other

Cat No Product Name / Activity
2459 Tropisetron hydrochloride
Activates α7Q79G-GlyR; also potent 5-HT3 antagonist and α7 nAChR partial agonist
3754 Varenicline tartrate
Potent activator of PSAM4-5-HT3 and PSAM4-GlyR; also selective α4β2 nAChR partial agonist

Pharmacologically Selective Effector Molecules (PSEMs) are inert ligands, that bind genetically-modified, chimeric ion channels, termed Pharmacologically Selective Actuator Modules (PSAMs), enabling control of cation, chloride or calcium conductance. PSAMs are based on research that demonstrates that the extracellular ligand binding domain of the α7 nicotinic ACh receptor (nAChR) can be transplanted onto the ion pore domain of other ligand gated ion channels. Splicing of the α7 nAChR ligand binding domain with the ion pore domain of the 5-HT3 receptor, for example, generates an ion channel with α7 nAChR pharmacology, but 5-HT3 cation conduction properties. Similarly, the α7 nAChR ligand binding domain has been spliced with the ion pore domain of the chloride selective glycine receptor (GlyR) to generate an ACh responsive chloride channel. Selective mutation of the α7 nAChR ligand binding domain has subsequently produced PSAM ion channels which show no/reduced ACh binding but are selectively bound by PSEMs.

PSAMs have been generated by the combination of the mutated α7 nAChR ligand binding domain (harboring a single, or multiple mutations) with the ion pore domain of several different ligand gated ion channels. These PSAM chimeras are named according to their mutations and linked ion pore domain: PSAML141F-GlyR, PSAML141F,Y115F-GlyR, PSAML141F,Y115F-5-HT3 and PSAML141F,Y115F-GABAC. 5-HT3 containing chimeras allow activation of neuronal activity, while GlyR and GABAC containing chimeras are inhibitory.


PSEMs Mechanism of Action

PSEMs Mechanism of Action.

Figure 1: Activating PSAMs are composed of a mutated α7 nAChR ligand binding domain spliced with the ion pore domain of a cation selective channel, such as 5-HT3. Binding of PSEMs to activating PSAMs results in influx of cations and activation of neuronal activity. Inhibitory PSAMs are composed of a mutated α7 nAChR ligand binding domain spliced with the ion pore domain of an anion selective channel, such as GlyR. Binding of PSEMs to inhibitory PSAMs results in influx of anions and inhibition of neuronal activity.

Literature for PSEMs

Tocris offers the following scientific literature for PSEMs to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


GPCR

GPCR Product Listing

A collection of over 450 products for G protein-coupled receptors, the listing includes research tools for the study of:

  • Rhodopsin-like Receptors
  • Glutamate Receptors
  • Frizzled Receptors
  • GPCR Signaling
Ion Channel

Ion Channel Product Listing

A collection of around 500 products for ion channel research, the listing includes research tools for the study of:

  • Ligand-gated ion channels
  • Voltage-gated ion channels
  • Other Ion Channels
Chemogenetics

Chemogenetics Research Bulletin

Produced by Tocris, the chemogenetics research bulletin provides an introduction to chemogenetic methods to manipulate neuronal activity. It outlines the development of RASSLs, DREADDs and PSAMs, and the use of chemogenetic compounds. DREADD ligands and PSEMs available from Tocris are highlighted.