PCP site 2 is a

binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...

that was identified as a high-

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

target Target may refer to: Physical items * Shooting target, used in marksmanship training and various shooting sports ** Bullseye (target), the goal one for which one aims in many of these sports ** Aiming point, in field artillery, f ...

for

phencyclidine Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted percept ...

(PCP), an

anesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...

and

dissociative hallucinogen Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...

that acts primarily as an

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

. The site is distinct from the PCP binding site on the NMDA receptor (otherwise known as PCP site 1) and the common/main sites on the

monoamine transporter Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT, DAT, NET) are responsible fo ...

s (, , ). It is associated with monoamine reuptake inhibition, and it has been suggested that the site may be an allosteric/regulatory site of the monoamine transporters. RTI-4793-14 (HBMP), a

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

with high affinity for the PCP site 2 and high

selectivity Selectivity may refer to: Psychology and behaviour * Choice, making a selection among options * Discrimination, the ability to recognize differences * Socioemotional selectivity theory, in social psychology Engineering * Selectivity (radio), a ...

for this site over the PCP site 1, has been developed. Similarly to PCP, RTI-4793-1 inhibits

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ar ...

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the Synapse, pre-synaptic neuron at a synapse) or glial cell after it has performed its function of ...

with moderate

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

, but unlike PCP, has very low potency as an NMDA receptor antagonist. It shows a profile of a

serotonin–norepinephrine–dopamine reuptake inhibitor A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, a ...

(SNDRI). Although this was inferred to be related to binding to the PCP site 2, subsequent research found that RTI-4793-14 also has considerable affinity for the DAT; it does not appear to have been characterized at the SERT or NET, but may bind to them similarly, and these interactions could potentially explain its monoamine reuptake inhibition as an alternative to the PCP site 2.

Activity profiles

References

{{Monoamine reuptake inhibitors Monoamine reuptake inhibitors