6′-Guanidinonaltrindole (6′-GNTI) is a κ– δ-
opioid receptor
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostati ...
selective ligand used in scientific research.
With 6′-GNTI, evidence was provided for the first time that receptor oligomerization plays functional role in living organisms.
6′-GNTI is an extremely
biased agonist
Functional selectivity (or agonist trafficking, biased agonism, biased signaling, ligand bias, and differential engagement) is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand (often the end ...
of the κ-opioid receptor. It is a potent
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...
of the
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...
pathway but does not recruit the
β-arrestin
Arrestins (abbreviated Arr) are a small family of proteins important for regulating signal transduction at G protein-coupled receptors.
Arrestins were first discovered in the late '80s as a part of a conserved two-step mechanism for regulatin ...
pathway. Due to its
functional selectivity
Functional selectivity (or agonist trafficking, biased agonism, biased signaling, ligand bias, and differential engagement) is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand (often the end ...
for the G protein pathway, 6′-GNTI functions as an
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. It is thought that 6′-GTNI may be able to produce
analgesia
Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...
without
dysphoria
Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation.
In psychiatry
Intense states of distress and uneas ...
RB-64
RB-64 is a semi-synthetic derivative of salvinorin A. It is an irreversible agonist, with a reactive thiocyanate group that forms a bond to the κ-opioid receptor (KOR), resulting in very high potency. It is functionally selective, activating ...
*
Noribogaine
Noribogaine (actually ''O''-desmethylibogaine), or 12-hydroxyibogamine, is the principal psychoactive metabolite of the oneirogen ibogaine. It is thought to be involved in the antiaddictive effects of ibogaine-containing plant extracts, such as ...