Tetrahydropalmatine
Encyclopedia
Tetrahydropalmatine is an alkaloid
found in several different plant species, mainly in the Corydalis
family, but also in other plants such as Stephania rotunda. These plants have traditional uses in Chinese herbal medicine. The pharmaceutical industry has synthetically produced the more potent enantiomer
Levo-tetrahydropalmatine (Levo-THP), which has been marketed worldwide under different brand names as an alternative to anxiolytic
and sedative
drugs of the benzodiazepine
group and analgesic
s such as opiate
s. It is also sold as a dietary supplement
.
and liver damage
. It is a blocker of voltage-activated L-type calcium channel active potasium channels. It is a potent muscle relaxant. It has also shown potential in the treatment of drug addiction to both cocaine
and opiates, and preliminary human studies have shown promising results.
Animal experiments have shown that the sedative effect of THP results from blocking dopaminergic
neurons in the brain
. Dopamine
is an important neurotransmitter
in the central nervous system
where it occurs in several important signaling systems that regulate muscular activity and attention, as well as feelings of joy, enthusiasm and creativity. Therefore, THP causes no feelings of euphoria
, and has been seen as an alternative to addictive
drugs for people suffering from anxiety and pain, and as a possibility for relief for people not helped by existing drugs.
, cardiac activity and the nervous system. In addition, chronic hepatitis
has been reported, caused by THP production in East Asia under conditions that were insufficiently sterile
. Fatalities started to be reported in 1999 in cases where THP had been used in combination with other drugs having analgesic and anti-anxiety effects. All 1999 deaths could be tied to a single THP-based supplement, sold under the name "Jin Bu Huan Anodyne Tablets". This product was therefore blacklisted by US and European health authorities. In some other countries, such as Singapore
, THP is treated as a controlled substance, and license is required to sell it.
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
found in several different plant species, mainly in the Corydalis
Corydalis
Corydalis is a genus of about 470 species of annual and perennial herbaceous plants in the fumewort family , native to the temperate Northern Hemisphere and the high mountains of tropical eastern Africa...
family, but also in other plants such as Stephania rotunda. These plants have traditional uses in Chinese herbal medicine. The pharmaceutical industry has synthetically produced the more potent enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
Levo-tetrahydropalmatine (Levo-THP), which has been marketed worldwide under different brand names as an alternative to anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
and sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
drugs of the benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
group and 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 ....
s such as opiate
Opiate
In medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant.-Overview:Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy,...
s. It is also sold as a dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
.
Effects
Tetrahydropalmatine has been demonstrated to possess analgesic effects and may be beneficial in the treatment of heart diseaseHeart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
and liver damage
Hepatotoxicity
Hepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...
. It is a blocker of voltage-activated L-type calcium channel active potasium channels. It is a potent muscle relaxant. It has also shown potential in the treatment of drug addiction to both cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
and opiates, and preliminary human studies have shown promising results.
Animal experiments have shown that the sedative effect of THP results from blocking dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
neurons in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. Dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
is an important neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
where it occurs in several important signaling systems that regulate muscular activity and attention, as well as feelings of joy, enthusiasm and creativity. Therefore, THP causes no feelings of euphoria
Euphoria (emotion)
Euphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of well-being, elation, happiness, ecstasy, excitement and joy...
, and has been seen as an alternative to addictive
Substance use disorder
Substance use disorders include substance abuse and substance dependence. In DSM-IV, the conditions are formally diagnosed as one or the other, but it has been proposed that DSM-5 combine the two into a single condition called "Substance-use disorder"....
drugs for people suffering from anxiety and pain, and as a possibility for relief for people not helped by existing drugs.
Cases of poisoning
Several cases of poisoning related to THP have been reported. These cases involved negative effects on respirationRespiration (physiology)
'In physiology, respiration is defined as the transport of oxygen from the outside air to the cells within tissues, and the transport of carbon dioxide in the opposite direction...
, cardiac activity and the nervous system. In addition, chronic hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
has been reported, caused by THP production in East Asia under conditions that were insufficiently sterile
Sterilization (microbiology)
Sterilization is a term referring to any process that eliminates or kills all forms of microbial life, including transmissible agents present on a surface, contained in a fluid, in medication, or in a compound such as biological culture media...
. Fatalities started to be reported in 1999 in cases where THP had been used in combination with other drugs having analgesic and anti-anxiety effects. All 1999 deaths could be tied to a single THP-based supplement, sold under the name "Jin Bu Huan Anodyne Tablets". This product was therefore blacklisted by US and European health authorities. In some other countries, such as Singapore
Singapore
Singapore , officially the Republic of Singapore, is a Southeast Asian city-state off the southern tip of the Malay Peninsula, north of the equator. An island country made up of 63 islands, it is separated from Malaysia by the Straits of Johor to its north and from Indonesia's Riau Islands by the...
, THP is treated as a controlled substance, and license is required to sell it.
See also
- ApomorphineApomorphineApomorphine is a non-selective dopamine agonist which activates both D1-like and D2-like receptors, with some preference for the latter subtypes. It is historically a morphine decomposition product by boiling with concentrated acid, hence the -morphine suffix...
- BulbocapnineBulbocapnineBulbocapnine is an alkaloid found in Corydalis and Dicentra, herbs in the family Fumariaceae that can cause fatal poisoning in sheep and cattle...
- GlaucineGlaucineGlaucine is an alkaloid found in several different plant species such as Glaucium flavum, Glaucium oxylobum, Croton lechleri and Corydalis yanhusuo. It has bronchodilator and antiinflammatory effects, acting as a PDE4 inhibitor and calcium channel blocker, and is used medically as an antitussive in...
- NantenineNantenineNantenine is an alkaloid found in the plant Nandina domestica as well as some Corydalis species. It is an antagonist at both the α1 adrenergic receptor and the 5-HT2A serotonin receptor, and blocks both the behavioural and physiological effects of MDMA in animals.-See...
- NuciferineNuciferineNuciferine is an alkaloid found within the plants Nymphaea caerulea and Nelumbo nucifera. It has a profile of action associated with dopamine receptor blockade. It induces catalepsy, it inhibits spontaneous motor activity, conditioned avoidance response, amphetamine toxicity and stereotypy...
- PukateinePukateinePukateine is an alkaloid found in the bark of the New Zealand tree Laurelia novae-zelandiae . An extract from pukatea is used in traditional Māori herbal medicine as an analgesic, and it is thought pukateine is the active component, as it is similar in both structure and activity to alkaloids such...
- StepholidineStepholidine-Stepholidine is a naturally occurring chemical compound found in the herb Stephania intermedia. Stepholidine is a dual D2 receptor antagonist and D1 receptor agonist, and has shown antipsychotic activity in animal studies.-See also:*Apomorphine...