Proglumide
Encyclopedia
Proglumide is a drug
that inhibits gastrointestinal motility
and reduces gastric secretions. It acts as a cholecystokinin antagonist
, which blocks both the CCKA
and CCKB
subtypes. It was used mainly in the treatment of stomach ulcers, although it has now been largely replaced by newer drugs for this application.
An interesting side effect of proglumide is that it enhances the analgesia produced by opioid
drugs, and can prevent or even reverse the development of tolerance to opioid drugs. This can make it a useful adjuvant
treatment to use alongside opioid drugs in the treatment of chronic pain conditions such as cancer, where opioid analgesics may be required for long periods and development of tolerance reduces clinical efficacy of these drugs.
Proglumide has also been shown to act as a δ-opioid
agonist, which may contribute to its analgesic effects.
Proglumide also works as a placebo effect amplifier for pain conditions. When injected visibly to a subject, its analgesic effect is bigger than a similarly administered placebo. When injected secretly, it does not have any effect, whereas standard pain drugs have an effect, even if they are administered without the subject's awareness. The supposed mechanism is an enhancement of the neural pathways of expectation.
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...
that inhibits gastrointestinal motility
Motility
Motility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. Most animals are motile but the term applies to single-celled and simple multicellular organisms, as well as to some mechanisms of fluid flow in multicellular organs, in...
and reduces gastric secretions. It acts as a cholecystokinin antagonist
Cholecystokinin antagonist
A Cholecystokinin antagonist is a specific type of receptor antagonist which blocks the receptor sites for the peptide hormone Cholecystokinin ....
, which blocks both the CCKA
Cholecystokinin A receptor
The extracellular, N-terminal, domain of this protein adopts a tertiary structure consisting of a few helical turns and a disulfide-cross linked loop...
and CCKB
Cholecystokinin B receptor
The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein that in humans is encoded by the CCKBR gene.This gene encodes a G protein-coupled receptor for gastrin and cholecystokinin , regulatory peptides of the brain and gastrointestinal tract...
subtypes. It was used mainly in the treatment of stomach ulcers, although it has now been largely replaced by newer drugs for this application.
An interesting side effect of proglumide is that it enhances the analgesia produced by opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
drugs, and can prevent or even reverse the development of tolerance to opioid drugs. This can make it a useful adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
treatment to use alongside opioid drugs in the treatment of chronic pain conditions such as cancer, where opioid analgesics may be required for long periods and development of tolerance reduces clinical efficacy of these drugs.
Proglumide has also been shown to act as a δ-opioid
Delta Opioid receptor
The δ-opioid receptors, also known as delta opioid receptor or simply delta receptor, abbreviated DOR, is an opioid receptor that has enkephalins as its endogenous ligands.-Function:...
agonist, which may contribute to its analgesic effects.
Proglumide also works as a placebo effect amplifier for pain conditions. When injected visibly to a subject, its analgesic effect is bigger than a similarly administered placebo. When injected secretly, it does not have any effect, whereas standard pain drugs have an effect, even if they are administered without the subject's awareness. The supposed mechanism is an enhancement of the neural pathways of expectation.