Lisdexamfetamine: Difference between revisions

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===Pharmacokinetics===

As a [[prodrug]], lisdexamfetamine is inactive in the form administered and ~~thus~~ lisdexamfetamine functions as an extended release version of ~~dextroamphetamine~~. Because D-amphetamine needs to ~~undergo hydrolysis to~~ from lysine via contact with ~~a yet unidentified aminopeptidase enzymes within~~ red blood cells~~. The~~ effects are independent of route of administration ~~due to the half-life~~ of lisdexamfetamine ~~being approximately 1~~-~~1.5 hours~~, slowing down the time ~~for D-Amphetamine~~ achieve peak concentrations and decreasing its magnitude and dampening consequent striatal dopamine release, which is thought to be responsible for its euphoric and [[compulsive redosing]] effects. Comparing lisdexamfetamine and D-amphetamine, the Tmax is ~4 hours for D-amphetamine from lisdexamfetamine metabolism. The Tlag is about 1 - 1.5 hours for D-Amphetamine from lisdexamfetamine.

As a [[prodrug]], lisdexamfetamine is inactive in the form administered. Once ingested, it is enzymatically cleaved into two parts: L-lysine, a naturally occurring essential amino acid, and d-amphetamine, a central nervous system stimulant. Thus lisdexamfetamine functions as an extended release version of dexamphetamine. Because d-amphetamine needs to be liberated from lysine via contact with red blood cells, effects are independent of route of administration. Conversion of lisdexamfetamine into active d-amphetamine is enzymatically [[Rate-Limiting Step|rate-limited]], slowing down the time to achieve peak concentrations and decreasing its magnitude and dampening consequent striatal dopamine release, which is thought to be responsible for its euphoric and [[compulsive redosing]] effects.

===Pharmacodymanics===

Amphetamine is a [[Agonist|full agonist]] of the trace amine-associated receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as [[dopamine]], [[serotonin]] and [[noradrenaline]].<ref>{{cite journal | vauthors=((Miller, G. M.)) | journal=Journal of neurochemistry | title=The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity | volume=116 | issue=2 | pages=164–176 | date= January 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/ | issn=0022-3042 | doi=10.1111/j.1471-4159.2010.07109.x}}</ref><ref>{{Citation |title=Drug banks amphetamine targets |url=http://www.drugbank.ca/drugs/DB00182#targets}}</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> The agonism of this set of receptors results in the release of increased concentrations of [[dopamine]], [[serotonin]] ~~(albiet weakly)~~ and [[noradrenaline]] in the [[synaptic cleft]]. This leads to [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.

Amphetamine is a [[Agonist|full agonist]] of the trace amine-associated receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as [[dopamine]], [[serotonin]] and [[noradrenaline]].<ref>{{cite journal | vauthors=((Miller, G. M.)) | journal=Journal of neurochemistry | title=The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity | volume=116 | issue=2 | pages=164–176 | date= January 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/ | issn=0022-3042 | doi=10.1111/j.1471-4159.2010.07109.x}}</ref><ref>{{Citation |title=Drug banks amphetamine targets |url=http://www.drugbank.ca/drugs/DB00182#targets}}</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> The agonism of this set of receptors results in the release of increased concentrations of [[dopamine]], [[serotonin]] and [[noradrenaline]] in the [[synaptic cleft]]. This leads to [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.

D-amphetamine's affinity for the TAAR1 receptor is twice that of L-amphetamine.<ref>{{cite journal | vauthors=((Lewin, A. H.)), ((Miller, G. M.)), ((Gilmour, B.)) | journal=Bioorganic & medicinal chemistry | title=Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | volume=19 | issue=23 | pages=7044–7048 | date=1 December 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/ | issn=0968-0896 | doi=10.1016/j.bmc.2011.10.007}}</ref> As a result, D-amphetamine produces three to four times as much central nervous system (CNS) stimulation as l-amphetamine. l-amphetamine, on the other hand, has stronger cardiovascular and peripheral effects.

d-amphetamine's affinity for the TAAR1 receptor is twice that of l-amphetamine.<ref>{{cite journal | vauthors=((Lewin, A. H.)), ((Miller, G. M.)), ((Gilmour, B.)) | journal=Bioorganic & medicinal chemistry | title=Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | volume=19 | issue=23 | pages=7044–7048 | date=1 December 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/ | issn=0968-0896 | doi=10.1016/j.bmc.2011.10.007}}</ref> As a result, d-amphetamine produces three to four times as much central nervous system (CNS) stimulation as l-amphetamine. l-amphetamine, on the other hand, has stronger cardiovascular and peripheral effects.

===Conversion rate===

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*'''[[Effect::Temporary erectile dysfunction]]'''

*'''[[Effect::Vasoconstriction]]'''

*'''[[Effect::Pain Relief]]''' <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791072/#:~:text=Clinical%20and%20in%20vivo%20lab,may%20possess%20some%20analgesic%20properties.&text=Qualitative%20studies%20have%20found%20that,methamphetamine%20to%20manage%20their%20pain.</ref>

*'''[[Effect::Numbness]]''' - This primarily occurs at high dosages in the limbs due to reduced blood flow and trouble circulating.

}}

@@ Line 21: / Line 21: @@
 ===Pharmacokinetics===
-As a [[prodrug]], lisdexamfetamine is inactive in the form administered and thus lisdexamfetamine functions as an extended release version of dextroamphetamine. Because D-amphetamine needs to undergo hydrolysis to from lysine via contact with a yet unidentified aminopeptidase enzymes within red blood cells. The effects are independent of route of administration due to the half-life of lisdexamfetamine being approximately 1-1.5 hours, slowing down the time for D-Amphetamine achieve peak concentrations and decreasing its magnitude and dampening consequent striatal dopamine release, which is thought to be responsible for its euphoric and [[compulsive redosing]] effects. Comparing lisdexamfetamine and D-amphetamine, the T<sub>max</sub> is  ~4 hours for D-amphetamine from lisdexamfetamine metabolism. The T<sub>lag</sub> is about 1 - 1.5 hours for D-Amphetamine from lisdexamfetamine.
+As a [[prodrug]], lisdexamfetamine is inactive in the form administered. Once ingested, it is enzymatically cleaved into two parts: L-lysine, a naturally occurring essential amino acid, and <small>d</small>-amphetamine, a central nervous system stimulant. Thus lisdexamfetamine functions as an extended release version of dexamphetamine. Because <small>d</small>-amphetamine needs to be liberated from lysine via contact with red blood cells, effects are independent of route of administration. Conversion of lisdexamfetamine into active <small>d</small>-amphetamine is enzymatically [[Rate-Limiting Step|rate-limited]], slowing down the time to achieve peak concentrations and decreasing its magnitude and dampening consequent striatal dopamine release, which is thought to be responsible for its euphoric and [[compulsive redosing]] effects.
 ===Pharmacodymanics===
-Amphetamine is a [[Agonist|full agonist]] of the trace amine-associated receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as [[dopamine]], [[serotonin]] and [[noradrenaline]].<ref>{{cite journal | vauthors=((Miller, G. M.)) | journal=Journal of neurochemistry | title=The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity | volume=116 | issue=2 | pages=164–176 | date= January 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/ | issn=0022-3042 | doi=10.1111/j.1471-4159.2010.07109.x}}</ref><ref>{{Citation |title=Drug banks amphetamine targets |url=http://www.drugbank.ca/drugs/DB00182#targets}}</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> The agonism of this set of receptors results in the release of increased concentrations of [[dopamine]], [[serotonin]] (albiet weakly) and [[noradrenaline]] in the [[synaptic cleft]]. This leads to [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.
+Amphetamine is a [[Agonist|full agonist]] of the trace amine-associated receptor 1 (TAAR1), which is a key regulator of common and trace brain monoamines such as [[dopamine]], [[serotonin]] and [[noradrenaline]].<ref>{{cite journal | vauthors=((Miller, G. M.)) | journal=Journal of neurochemistry | title=The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity | volume=116 | issue=2 | pages=164–176 | date= January 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/ | issn=0022-3042 | doi=10.1111/j.1471-4159.2010.07109.x}}</ref><ref>{{Citation |title=Drug banks amphetamine targets |url=http://www.drugbank.ca/drugs/DB00182#targets}}</ref><ref>TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364</ref> The agonism of this set of receptors results in the release of increased concentrations of [[dopamine]], [[serotonin]] and [[noradrenaline]] in the [[synaptic cleft]]. This leads to [[Thought acceleration|cognitive]] and [[Stimulation|physical stimulation]] within the user.
-D-amphetamine's affinity for the TAAR1 receptor is twice that of L-amphetamine.<ref>{{cite journal | vauthors=((Lewin, A. H.)), ((Miller, G. M.)), ((Gilmour, B.)) | journal=Bioorganic & medicinal chemistry | title=Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | volume=19 | issue=23 | pages=7044–7048 | date=1 December 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/ | issn=0968-0896 | doi=10.1016/j.bmc.2011.10.007}}</ref> As a result, D-amphetamine produces three to four times as much central nervous system (CNS) stimulation as <small>l</small>-amphetamine. <small>l</small>-amphetamine, on the other hand, has stronger cardiovascular and peripheral effects.
+<small>d</small>-amphetamine's affinity for the TAAR1 receptor is twice that of <small>l</small>-amphetamine.<ref>{{cite journal | vauthors=((Lewin, A. H.)), ((Miller, G. M.)), ((Gilmour, B.)) | journal=Bioorganic & medicinal chemistry | title=Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | volume=19 | issue=23 | pages=7044–7048 | date=1 December 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236098/ | issn=0968-0896 | doi=10.1016/j.bmc.2011.10.007}}</ref> As a result, <small>d</small>-amphetamine produces three to four times as much central nervous system (CNS) stimulation as <small>l</small>-amphetamine. <small>l</small>-amphetamine, on the other hand, has stronger cardiovascular and peripheral effects.
 ===Conversion rate===
@@ Line 63: / Line 63: @@
 *'''[[Effect::Temporary erectile dysfunction]]'''
 *'''[[Effect::Vasoconstriction]]'''
+*'''[[Effect::Pain Relief]]''' <ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791072/#:~:text=Clinical%20and%20in%20vivo%20lab,may%20possess%20some%20analgesic%20properties.&text=Qualitative%20studies%20have%20found%20that,methamphetamine%20to%20manage%20their%20pain.</ref>
+*'''[[Effect::Numbness]]''' - This primarily occurs at high dosages in the limbs due to reduced blood flow and trouble circulating.
 }}