Herkinorin
Encyclopedia
Herkinorin is an opioid
analgesic
that is an analogue
of the natural product Salvinorin A
. It was discovered in 2005 during structure-activity relationship studies into neoclerodane diterpenes, the family of chemical compounds of which Salvinorin A is a member.
Unlike Salvinorin A which is a selective κ-opioid
agonist
with no significant μ-opioid
receptor
affinity, herkinorin is a μ-opioid agonist with more than 100x higher μ-opioid affinity and 50x lower κ-opioid affinity compared to Salvinorin A. Herkinorin is a semi-synthetic compound, made from Salvinorin B, which is most conveniently made from Salvinorin A by deacetylation, as while both Salvinorin A and Salvinorin B are found in the plant Salvia divinorum
, Salvinorin A is present in larger quantities.
A study in primates showed it to act as both a peripherally active μ and κ agonist with a fast onset of action. The study did not find any evidence of central activity in primates and questions whether herkinorin's effects are due entirely to peripheral binding. Unlike most μ-opioid agonists, herkinorin does not promote the recruitment of β-arrestin-2
to the intracellular domain of the μ-opioid receptor, or induce receptor internalization
. This means that herkinorin may not produce tolerance and dependence in the same way as other opioids, although some development of tolerance through other mechanisms has been observed, and some other analogues related to herkinorin can recruit β-arrestins.
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...
analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
that is an analogue
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of the natural product Salvinorin A
Salvinorin A
Salvinorin A is the main active psychotropic molecule in Salvia divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans...
. It was discovered in 2005 during structure-activity relationship studies into neoclerodane diterpenes, the family of chemical compounds of which Salvinorin A is a member.
Unlike Salvinorin A which is a selective κ-opioid
Kappa Opioid receptor
The κ-opioid receptor is a protein that in humans is encoded by the OPRK1 gene. The κ-opioid receptor is one of five related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds...
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...
with no significant μ-opioid
Mu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
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...
affinity, herkinorin is a μ-opioid agonist with more than 100x higher μ-opioid affinity and 50x lower κ-opioid affinity compared to Salvinorin A. Herkinorin is a semi-synthetic compound, made from Salvinorin B, which is most conveniently made from Salvinorin A by deacetylation, as while both Salvinorin A and Salvinorin B are found in the plant Salvia divinorum
Salvia divinorum
Salvia divinorum is a psychoactive plant which can induce dissociative effects and is a potent producer of "visions" and other hallucinatory experiences...
, Salvinorin A is present in larger quantities.
A study in primates showed it to act as both a peripherally active μ and κ agonist with a fast onset of action. The study did not find any evidence of central activity in primates and questions whether herkinorin's effects are due entirely to peripheral binding. Unlike most μ-opioid agonists, herkinorin does not promote the recruitment of β-arrestin-2
Arrestin
Arrestins are a small family of proteins important for regulating signal transduction.-Function:Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors in the visual rhodopsin system by Hermann Kühn and co-workers and...
to the intracellular domain of the μ-opioid receptor, or induce receptor internalization
Receptor-mediated endocytosis
Receptor-mediated endocytosis , also called clathrin-dependent endocytosis, is a process by which cells internalize molecules by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules being internalized.-Process:After the binding of a...
. This means that herkinorin may not produce tolerance and dependence in the same way as other opioids, although some development of tolerance through other mechanisms has been observed, and some other analogues related to herkinorin can recruit β-arrestins.
See also
- 2-Ethoxymethyl Salvinorin B2-Ethoxymethyl Salvinorin B2-Ethoxymethyl salvinorin B is a semi-synthetic analogue of the natural product salvinorin A, with a longer duration of action of around 3 hours , and increased affinity and intrinsic activity at the κ-opioid receptor...
- 2-Methoxymethyl Salvinorin B2-Methoxymethyl Salvinorin B2-Methoxymethyl salvinorin B is a semi-synthetic analogue of the natural product salvinorin A which is used in scientific research. It has a longer duration of action of around 2–3 hours, compared to less than 30 minutes for salvinorin A, and has increased affinity and efficacy at the κ-opioid...
- Salvinorin ASalvinorin ASalvinorin A is the main active psychotropic molecule in Salvia divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans...