PRX-00023
Encyclopedia
PRX-00023 is a drug
of the phenylpiperazine
class that was being developed by EPIX Pharmaceuticals Inc
for the treatment of generalized anxiety disorder and major depressive disorder. It was well tolerated in clinical trial
s but failed to reach significant remission on the Hammilton Rating Scales
and development was subsequently discontinued.
PRX-00023 acts as a selective
5-HT1A receptor
ligand
and σ receptor
agonist
. Originally believed to have appreciable intrinsic activity
as an agonist
of the 5-HT1A receptor, later studies found it to possess very low efficacy (6-7% relative to 5-HT
) and to behave more like an antagonist
, likely underlying its failure as an antidepressant
/anxiolytic
in clinical trials.
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
of the phenylpiperazine
Phenylpiperazine
1-Phenylpiperazine is a simple chemical compound featuring a phenyl group bound to a piperazine ring. The suffix '-piprazole' is sometimes used in the names of drugs to indicate they belong to this class....
class that was being developed by EPIX Pharmaceuticals Inc
EPIX Pharmaceuticals Inc
EPIX Pharmaceuticals Inc was a pharmaceutical company based in Lexington, Massachusetts.Its products included the following agents:...
for the treatment of generalized anxiety disorder and major depressive disorder. It was well tolerated in clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s but failed to reach significant remission on the Hammilton Rating Scales
Hamilton Depression Rating Scale
The Hamilton Rating Scale for Depression , also known as the Hamilton Depression Rating Scale or abbreviated to HAM-D, is a multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. Max Hamilton originally published the scale in 1960 and reviewed...
and development was subsequently discontinued.
PRX-00023 acts as a selective
Functional Selectivity
Functional selectivity is the ligand-dependent selectivity for certain signal transduction pathways in one and the same receptor. This can be present when a receptor has several possible signal transduction pathways...
5-HT1A receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
and σ receptor
Sigma receptor
The sigma receptors σ1 and σ2 bind to ligands such as 4-PPBP, SA 4503, ditolylguanidine, dimethyltryptamine and siramesine.- Classification :...
agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
. Originally believed to have appreciable intrinsic activity
Intrinsic activity
Intrinsic activity or efficacy refers to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its molecular target, and the EC50, which is a measure of the...
as an agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
of the 5-HT1A receptor, later studies found it to possess very low efficacy (6-7% relative to 5-HT
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
) and to behave more like an antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
, likely underlying its failure as an antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
/anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
in clinical trials.