Talk:L-DOPA: Difference between revisions

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'''L-DOPA''' (also known as '''levodopa''' and '''L-3,4-dihydroxyphenylalanine''') is an amino acid, dietary supplement and weak [[Psychoactive class::stimulant]]. It is found primarily in the seeds of the plant ''Mucuna pruriens'', also known as the velvet bean or monkey tamarind, making up 3.1–6.1% of the seeds' dry weight.<ref name="toxicology">{{cite book |last1=Dart |first1=Richard C. |url=https://books.google.com/books?id=qDf3AO8nILoC&q=%22mucuna+pruriens%22+alkaloids&pg=PA1679 |title=Medical Toxicology - Google Book Search |year=2004 |isbn=978-0-7817-2845-4 |access-date=2008-03-15}}</ref>

It is produced from and closely related to the ~~non-essential~~ amino acids L-phenylalanine and [[Tyrosine|L-tyrosine]] via the [[wikipedia:Biopterin-dependent aromatic amino acid hydroxylase|AAAH]] enzyme, and is itself a precursor to the catecholamine neurotransmitters [[Dopamine|dopamine]], [[Norepinephrine|norepinephrine]] and [[Epinephrine|adrenaline]] via the enzymes [[wikipedia:Aromatic L-amino acid decarboxylase|AADC]], [[wikipedia:Dopamine beta-hydroxylase|DBH]] and [[wikipedia:Phenylethanolamine N-methyltransferase|PNMT]].<ref name="Trace amine template 1">{{cite journal | vauthors = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacology & Therapeutics| volume = 125 | issue = 3 | pages = 363–375 | date = March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005}}</ref> It also mediates release of neurotrophic factor.<ref>{{cite journal | vauthors = Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS | title = L-DOPA is an endogenous ligand for OA1 | journal = PLOS Biology | volume = 6 | issue = 9 | pages = e236 | date = September 2008 | pmid = 18828673 | pmc = 2553842 | doi = 10.1371/journal.pbio.0060236 }}</ref> Thus, supplementing with L-DOPA has neuroprotective effects and increaseslevels of catecholamines in the central nervous system, while not acting as a releasing agent of reuptake inhibitor of them, like how typical stimulants such as [[ecstasy|MDMA]] and [[cocaine]] act. Because of this, and its short duration of action, it can be considered an atypical stimulant.

It is produced from and closely related to the amino acids L-phenylalanine and [[Tyrosine|L-tyrosine]], which are essential and nonessential respectively, via the [[wikipedia:Biopterin-dependent aromatic amino acid hydroxylase|AAAH]] enzyme, and is itself a precursor to the catecholamine neurotransmitters [[Dopamine|dopamine]], [[Norepinephrine|norepinephrine]] and [[Epinephrine|adrenaline]] via the enzymes [[wikipedia:Aromatic L-amino acid decarboxylase|AADC]], [[wikipedia:Dopamine beta-hydroxylase|DBH]] and [[wikipedia:Phenylethanolamine N-methyltransferase|PNMT]].<ref name="Trace amine template 1">{{cite journal | vauthors = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacology & Therapeutics| volume = 125 | issue = 3 | pages = 363–375 | date = March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005}}</ref> It also mediates release of neurotrophic factor.<ref>{{cite journal | vauthors = Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS | title = L-DOPA is an endogenous ligand for OA1 | journal = PLOS Biology | volume = 6 | issue = 9 | pages = e236 | date = September 2008 | pmid = 18828673 | pmc = 2553842 | doi = 10.1371/journal.pbio.0060236 }}</ref> Thus, supplementing with L-DOPA has neuroprotective effects and increaseslevels of catecholamines in the central nervous system, while not acting as a releasing agent of reuptake inhibitor of them, like how typical stimulants such as [[ecstasy|MDMA]] and [[cocaine]] act. Because of this, and its short duration of action, it can be considered an atypical stimulant.

L-DOPA is available as a prescription-only drug and a main-line treatment for Parkinson's disease and dopamine-responsive dystonia. It is also used as a [[nootropic]] or recreationally. Both of these uses are more commonly through consumption of the seeds of ''Mucuna pruriens'' than in pure crystalline form. [[Subjective effects]] of ''Mucuna pruriens'' include [[stimulation]], [[wakefulness]], [[focus enhancement]], [[analysis enhancement]], and [[motivation enhancement]].

== History and culture ==

WIP

== Chemistry ==

'''L-DOPA''', also known as '''L-3,4-dihydroxyphenylalanine''', is an amino acid. The chemical structure of L-DOPA contains the structure of L-phenylalanine, itself alanine with a phenyl group attached to the end, with two additional hydroxy groups on the "3" and "4" positions of the benzene ring. This is analogous to how dopamine, the primary metabolite of L-dopa, contains the structure of [[phenethylamine]], the primary metabolite of L-phenylalanine, with two additional hydroxy groups on the "3" and "4" positions of the benzene ring, and thus indicates that L-DOPA possesses dopaminergic activity. The name L-DOPA is a contraction from '''l'''evo'''-d'''ihydr'''o'''xy'''p'''henyl'''a'''lanine'''.

It is the precursor to the catecholamines, neurotransmitters and sympathomimetic amines containing a dihydroxybenzene (catechol) group attached to a monoamine side chain.

The enantiomer, '''D-DOPA''' of L-DOPA is biologically inactive and does not seem to naturally occur.

== Pharmacology ==

L-DOPA exerts its effects by increasing levels of the [[neurotransmitters]] [[norepinephrine]] and [[dopamine]] in the synapses of central nervous system. While other stimulants do this by causing these neurotransmitters to be released from the presynaptic neuron into the synapse; preventing the proteins DAT & NET from reabsorbing neurotransmitters already in the synapse; or preventing the enzymes MAO-A & MAO-B from oxidizing and thus inactivating neurotransmitters already in the synapse, L-DOPA directly increasing levels of dopamine and norepinephrine which are produced by the body.

Further stimulatory and euphoric effects of L-DOPA are caused by it binding to the dopamine receptors D(1A), D(2) and D(4) and the [[Serotonin#The 5-HT system|serotonin receptors]] 5-HT2A, 5-HT2C, and 5-HT3A: analogously to [[methamphetamine]], [[LSD]] or [[Harmala alkaloid|harmine]].<ref name="bindingdb">[https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=4377]</ref>

L-DOPA also weakly inhibits:

- ABCC2, ABCC3, ABCC4, leading to increased levels of adenosine triphosphate (ATP), the primary energy source of the body.<ref name="atp">{{cite journal | vauthors = Ryan E. Morgan and others | title = A Multifactorial Approach to Hepatobiliary Transporter Assessment Enables Improved Therapeutic Compound Development | journal = Toxicological Sciences| volume = 136 | issue = 1 | pages = 216–241 | date = November 2013}}</ref>

- In mushrooms, tyrosinase, leading to decreased levels of melanin and increased levels of tyrosine.<ref name="tyrosinase">{{cite journal | vauthors = Ken-ichi Nihei, Isao Kubo | title = Identification of oxidation product of arbutin in mushroom tyrosinase assay system | journal = Bioorganic & Medicinal Chemistry Letters| volume = 13 | issue = 14 | pages = 2409-2412 | date = 21 July 2003}}</ref>

- Xanthine dehydrogenase & oxidase, leading to increased levels of xanthine.

== Subjective effects ==

== Toxicity and harm potential ==

== Legal status ==

- Australia: Possession, cultivation and distribution of Mucuna pruriens is legal. Pure L-DOPA is prescription-only.

- United Kingdom: Possession, cultivation and distribution of Mucuna pruriens, and possession of pure L-DOPA for personal use, is legal. Distribution of L-DOPA in its pure form, unless by a licensed pharmacist to a patient with a prescription, is illegal under the Medicines Act 1968.

- United States: Possession, cultivation and distribution of Mucuna pruriens, and possession and distribution of certain products containing L-DOPA, is legal. Many other forms of L-DOPA are prescription-only.

- European Union: Pure L-DOPA is prescription-only.

== References ==

@@ Line 4: / Line 4: @@
 '''L-DOPA''' (also known as '''levodopa''' and '''L-3,4-dihydroxyphenylalanine''') is an amino acid, dietary supplement and weak [[Psychoactive class::stimulant]]. It is found primarily in the seeds of the plant ''Mucuna pruriens'', also known as the velvet bean or monkey tamarind, making up 3.1–6.1% of the seeds' dry weight.<ref name="toxicology">{{cite book |last1=Dart |first1=Richard C. |url=https://books.google.com/books?id=qDf3AO8nILoC&q=%22mucuna+pruriens%22+alkaloids&pg=PA1679 |title=Medical Toxicology - Google Book Search |year=2004 |isbn=978-0-7817-2845-4 |access-date=2008-03-15}}</ref>
-It is produced from and closely related to the non-essential amino acids L-phenylalanine and [[Tyrosine|L-tyrosine]] via the [[wikipedia:Biopterin-dependent aromatic amino acid hydroxylase|AAAH]] enzyme, and is itself a precursor to the catecholamine neurotransmitters [[Dopamine|dopamine]], [[Norepinephrine|norepinephrine]] and [[Epinephrine|adrenaline]] via the enzymes [[wikipedia:Aromatic L-amino acid decarboxylase|AADC]], [[wikipedia:Dopamine beta-hydroxylase|DBH]] and [[wikipedia:Phenylethanolamine N-methyltransferase|PNMT]].<ref name="Trace amine template 1">{{cite journal | vauthors = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacology & Therapeutics| volume = 125 | issue = 3 | pages = 363–375 | date = March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005}}</ref> It also mediates release of neurotrophic factor.<ref>{{cite journal | vauthors = Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS | title = L-DOPA is an endogenous ligand for OA1 | journal = PLOS Biology | volume = 6 | issue = 9 | pages = e236 | date = September 2008 | pmid = 18828673 | pmc = 2553842 | doi = 10.1371/journal.pbio.0060236 }}</ref> Thus, supplementing with L-DOPA has neuroprotective effects and increaseslevels of catecholamines in the central nervous system, while not acting as a releasing agent of reuptake inhibitor of them, like how typical stimulants such as [[ecstasy|MDMA]] and [[cocaine]] act. Because of this, and its short duration of action, it can be considered an atypical stimulant.
+It is produced from and closely related to the amino acids L-phenylalanine and [[Tyrosine|L-tyrosine]], which are essential and nonessential respectively, via the [[wikipedia:Biopterin-dependent aromatic amino acid hydroxylase|AAAH]] enzyme, and is itself a precursor to the catecholamine neurotransmitters [[Dopamine|dopamine]], [[Norepinephrine|norepinephrine]] and [[Epinephrine|adrenaline]] via the enzymes [[wikipedia:Aromatic L-amino acid decarboxylase|AADC]], [[wikipedia:Dopamine beta-hydroxylase|DBH]] and [[wikipedia:Phenylethanolamine N-methyltransferase|PNMT]].<ref name="Trace amine template 1">{{cite journal | vauthors = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacology & Therapeutics| volume = 125 | issue = 3 | pages = 363–375 | date = March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005}}</ref> It also mediates release of neurotrophic factor.<ref>{{cite journal | vauthors = Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS | title = L-DOPA is an endogenous ligand for OA1 | journal = PLOS Biology | volume = 6 | issue = 9 | pages = e236 | date = September 2008 | pmid = 18828673 | pmc = 2553842 | doi = 10.1371/journal.pbio.0060236 }}</ref> Thus, supplementing with L-DOPA has neuroprotective effects and increaseslevels of catecholamines in the central nervous system, while not acting as a releasing agent of reuptake inhibitor of them, like how typical stimulants such as [[ecstasy|MDMA]] and [[cocaine]] act. Because of this, and its short duration of action, it can be considered an atypical stimulant.
 L-DOPA is available as a prescription-only drug and a main-line treatment for Parkinson's disease and dopamine-responsive dystonia. It is also used as a [[nootropic]] or recreationally. Both of these uses are more commonly through consumption of the seeds of ''Mucuna pruriens'' than in pure crystalline form. [[Subjective effects]] of ''Mucuna pruriens'' include [[stimulation]], [[wakefulness]], [[focus enhancement]], [[analysis enhancement]], and [[motivation enhancement]].
+== History and culture ==
+WIP
+== Chemistry ==
+'''L-DOPA''', also known as '''L-3,4-dihydroxyphenylalanine''', is an amino acid. The chemical structure of L-DOPA contains the structure of L-phenylalanine, itself alanine with a phenyl group attached to the end, with two additional hydroxy groups on the "3" and "4" positions of the benzene ring. This is analogous to how dopamine, the primary metabolite of L-dopa, contains the structure of [[phenethylamine]], the primary metabolite of L-phenylalanine, with two additional hydroxy groups on the "3" and "4" positions of the benzene ring, and thus indicates that L-DOPA possesses dopaminergic activity. The name L-DOPA is a contraction from '''<u>l</u>'''evo'''-<u>d</u>'''ihydr'''<u>o</u>'''xy'''<u>p</u>'''henyl'''<u>a</u>'''lanine'''.
+It is the precursor to the catecholamines, neurotransmitters and sympathomimetic amines containing a dihydroxybenzene (catechol) group attached to a monoamine side chain.
+The enantiomer, '''D-DOPA''' of L-DOPA is biologically inactive and does not seem to naturally occur.
+== Pharmacology ==
+L-DOPA exerts its effects by increasing levels of the [[neurotransmitters]] [[norepinephrine]] and [[dopamine]] in the synapses of central nervous system. While other stimulants do this by causing these neurotransmitters to be released from the presynaptic neuron into the synapse; preventing the proteins DAT & NET from reabsorbing neurotransmitters already in the synapse; or preventing the enzymes MAO-A & MAO-B from oxidizing and thus inactivating neurotransmitters already in the synapse, L-DOPA directly increasing levels of dopamine and norepinephrine which are produced by the body.
+Further stimulatory and euphoric effects of L-DOPA are caused by it binding to the dopamine receptors D(1A), D(2) and D(4) and the [[Serotonin#The 5-HT system|serotonin receptors]] 5-HT<sub>2A</sub>, 5-HT<sub>2C</sub>, and 5-HT<sub>3A</sub>: analogously to [[methamphetamine]], [[LSD]] or [[Harmala alkaloid|harmine]].<ref name="bindingdb">[https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=4377]</ref>
+L-DOPA also weakly inhibits:
+- ABCC2, ABCC3, ABCC4, leading to increased levels of adenosine triphosphate (ATP), the primary energy source of the body.<ref name="atp">{{cite journal | vauthors = Ryan E. Morgan and others | title = A Multifactorial Approach to Hepatobiliary Transporter Assessment Enables Improved Therapeutic Compound Development | journal = Toxicological Sciences| volume = 136 | issue = 1 | pages = 216–241 | date = November 2013}}</ref>
+- In mushrooms, tyrosinase, leading to decreased levels of melanin and increased levels of tyrosine.<ref name="tyrosinase">{{cite journal | vauthors = Ken-ichi Nihei, Isao Kubo | title = Identification of oxidation product of arbutin in mushroom tyrosinase assay system | journal = Bioorganic & Medicinal Chemistry Letters| volume = 13 | issue = 14 | pages = 2409-2412 | date = 21 July 2003}}</ref>
+- Xanthine dehydrogenase & oxidase, leading to increased levels of xanthine.
+== Subjective effects ==
+== Toxicity and harm potential ==
+== Legal status ==
+- Australia: Possession, cultivation and distribution of Mucuna pruriens is legal. Pure L-DOPA is prescription-only.
+- United Kingdom: Possession, cultivation and distribution of Mucuna pruriens, and possession of pure L-DOPA for personal use, is legal. Distribution of L-DOPA in its pure form, unless by a licensed pharmacist to a patient with a prescription, is illegal under the Medicines Act 1968.
+- United States: Possession, cultivation and distribution of Mucuna pruriens, and possession and distribution of certain products containing L-DOPA, is legal. Many other forms of L-DOPA are prescription-only.
+- European Union: Pure L-DOPA is prescription-only.
 <br />
+== References ==
 <references />