Tetrahydropalmatine (THP) is an isoquinoline alkaloid found in several different plant species, mainly in the genus '' Corydalis'' ( Yan Hu Suo), 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 An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

and sedative drugs of the benzodiazepine group and analgesics such as opiates. It is also sold as a dietary supplement. In 1940, a

Vietnam Vietnam or Viet Nam ( vi, Việt Nam, ), officially the Socialist Republic of Vietnam,., group="n" is a country in Southeast Asia, at the eastern edge of mainland Southeast Asia, with an area of and population of 96 million, making i ...

ese scientist Sang Dinh Bui extracted an

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

from the root of '' Stephania rotunda'' with the yield of 1.2 - 1.5% and he named this compound rotundine. From 1950 to 1952, two Indian scientists studied and extracted from ''

Stephania glabra ''Stephania'' is a genus of flowering plants in the family Menispermaceae, native to eastern and southern Asia and Australia. They are herbaceous perennial vines, growing to around four metres tall, with a large tuber. The leaves are arranged s ...

'' another

named hyndanrine. In 1965, the structure of rotundine and hyndarin was proved to be the same as tetrahydropalmatine.

Effects

Tetrahydropalmatine has been demonstrated to possess analgesic effects and may be beneficial in the treatment of heart disease and

liver damage Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the si ...

. It is a blocker of voltage-activated L-type calcium channel active potassium channels. It is a potent muscle relaxant. It has also shown potential in the treatment of

drug addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...

to both

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...

and

opiates An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonist ...

, and preliminary human studies have shown promising results. The pharmacological profile of l-THP includes antagonism of dopamine D1, and D2 receptors as well as actions at dopamine D3, alpha adrenergic and serotonin receptors. The Ki values for l-THP at D1 and D2 dopamine receptors are approximately 124 nM (D1) and 388 nM (D2). In addition to the antagonism of post-synaptic dopamine receptors, the blockade of pre-synaptic autoreceptors by l-THP results in increased dopamine release, and it has been suggested that lower affinity of l-THP for D2 receptors may confer some degree of autoreceptor selectivity. Along with dopamine receptors, l-THP has been reported to interact with a number of other receptor types, including alpha-1 adrenergic receptors, at which it functions as an antagonist, and GABA-A receptors, through positive allosteric modulation. Additionally, l-THP displays significant binding to 5-HT1A and alpha-2 adrenergic receptors. In the case of 5-HT1A receptors, l-THP binds with a Ki of approximately 340 nM. Animal experiments have shown that the sedative effect of THP results from blocking dopaminergic neurons in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

. Dopamine is an important neurotransmitter in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

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.

Cases of poisoning

Several cases of poisoning related to THP have been reported. These cases involved negative effects on

respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellul ...

cardiac The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

activity, and the nervous system. In addition, chronic

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...

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 Singapore (), officially the Republic of Singapore, is a sovereign island country and city-state in maritime Southeast Asia. It lies about one degree of latitude () north of the equator, off the southern tip of the Malay Peninsula, bor ...

, THP is treated as a controlled substance, and license is required to sell it.

References

{{Dopamine receptor modulators

External links

Introduction to Rotundine
Adrenergic receptor modulators Alpha-1 blockers Benzylisoquinoline alkaloids D1 antagonists D2 antagonists Dopamine receptor modulators GABAA receptor positive allosteric modulators Ion channel blockers Phenol ethers Plant toxins Serotonin receptor modulators

Effects

Cases of poisoning

See also

References

External links