Positive allosteric modulator

Positive allosteric modulator (PAM) is a type of pharmacological agent that enhances the activity of a protein or receptor by binding to a site different from the active site. This binding results in a change in the protein's conformation, or shape, which increases the efficacy or potency of the endogenous ligand.

Mechanism of Action

PAMs work by binding to allosteric sites on a protein. These sites are distinct from the active site where the endogenous ligand binds. When a PAM binds to an allosteric site, it changes the conformation of the protein, which can enhance the binding of the endogenous ligand to the active site. This can result in an increase in the activity of the protein or receptor.

PAMs do not have any effect on their own, but they enhance the effect of the endogenous ligand. This is in contrast to orthosteric ligands, which can activate or inhibit a protein or receptor directly.

Applications

Positive allosteric modulators have a wide range of potential applications in medicine and drug discovery. They can be used to enhance the activity of proteins or receptors that are underactive in certain diseases or conditions. For example, PAMs of the GABA receptor are being investigated for the treatment of anxiety disorders and epilepsy.

PAMs can also be used to enhance the effect of drugs. For example, a PAM of a opioid receptor could potentially enhance the pain-relieving effect of an opioid drug, allowing for lower doses to be used and reducing the risk of side effects and addiction.

See Also

• Allosteric regulation
• Negative allosteric modulator
• Pharmacology
• Drug discovery