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{{Drugbox
{{Drugbox
| IUPAC_name = 1-(5-chloro-1H-indol-3-yl)propan-2-amine
| IUPAC_name = 1-(5-Chloro-1H-indol-3-yl)propan-2-amine
| image = 5-Chloro-3-(2-aminopropyl)indole.svg
| image = 5-Chloro-3-(2-aminopropyl)indole.svg
| CAS_number = 712-07-2
| CAS_number = 712-07-2
Line 35: Line 35:
5-Chloro-αMT was found to not reliably produce [[intracranial]] [[self-administration]] in rats or substitute for [[cocaine]] in rats or monkeys.<ref name="pmid24796848" /> It was found through study of 5-chloro-αMT in [[rhesus monkey]]s that norepinephrine release has minimal influence on the [[abuse potential]] of [[monoamine releasing agent]]s and that loss of norepinephrine release activity does not affect [[Efficacy#Medicine|efficacy]] in reducing cocaine self-administration in SDRAs relative to [[serotonin-norepinephrine-dopamine releasing agent]]s (SNDRAs) such as [[naphthylisopropylamine]] (PAL-287).<ref name="pmid24796848" /> However, SDRAs like PAL-542 would, in theory, be expected to produce fewer [[side effect]]s (including [[sympathomimetic]]/[[cardiovascular]] effects, [[insomnia]], [[hyperthermia]], and [[anxiety]]) relative to SNDRAs, and thus would likely be comparatively more favorable in the treatment of cocaine dependence and other conditions.<ref name="pmid24796848" />
5-Chloro-αMT was found to not reliably produce [[intracranial]] [[self-administration]] in rats or substitute for [[cocaine]] in rats or monkeys.<ref name="pmid24796848" /> It was found through study of 5-chloro-αMT in [[rhesus monkey]]s that norepinephrine release has minimal influence on the [[abuse potential]] of [[monoamine releasing agent]]s and that loss of norepinephrine release activity does not affect [[Efficacy#Medicine|efficacy]] in reducing cocaine self-administration in SDRAs relative to [[serotonin-norepinephrine-dopamine releasing agent]]s (SNDRAs) such as [[naphthylisopropylamine]] (PAL-287).<ref name="pmid24796848" /> However, SDRAs like PAL-542 would, in theory, be expected to produce fewer [[side effect]]s (including [[sympathomimetic]]/[[cardiovascular]] effects, [[insomnia]], [[hyperthermia]], and [[anxiety]]) relative to SNDRAs, and thus would likely be comparatively more favorable in the treatment of cocaine dependence and other conditions.<ref name="pmid24796848" />


A related agent, [[5-fluoro-α-methyltryptamine]] (5-fluoro-αMT), also known as PAL-544, is a potent [[MAO-A inhibitor]] in addition to SNDRA and 5-HT<sub>2A</sub> receptor agonist.<ref name="pmid24796848" /><ref name="pmid3797802">{{cite journal | author = Kinemuchi H, Arai Y | title = Selective inhibition of monoamine oxidase A and B by two substrate-analogues, 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methylphenethylamine | journal = Res. Commun. Chem. Pathol. Pharmacol. | volume = 54 | issue = 1 | pages = 125–8 |date=October 1986 | pmid = 3797802 | doi = | url = }}</ref><ref name="pmid25193229" /> Due to their close [[chemical structure|structural]] similarity, 5-chloro-αMT might also possess activity as an MAO-A inhibitor, a property which, in combination with its activity as [[monoamine releasing agent]], could potentially render it dangerous in an analogous manner to the [[substituted phenethylamine|phenethylamine]] derivative [[para-Methoxyamphetamine|''para''-methoxyamphetamine]] (PMA).<ref name="pmid11041537">{{cite journal | author = Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F | title = Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat | journal = Progress in Neuro-psychopharmacology & Biological Psychiatry | volume = 24 | issue = 6 | pages = 955–77 |date=August 2000 | pmid = 11041537 | doi = 10.1016/S0278-5846(00)00113-5| url = http://linkinghub.elsevier.com/retrieve/pii/S0278-5846(00)00113-5}}</ref> In addition, [[α-ethyltryptamine]] (αET), an SNDRA and close [[structural analog]] of αMT and 5-chloro-αMT, like many other [[releasing agent]]s of both 5-HT and DA such as [[3,4-methylenedioxy-N-methylamphetamine|MDMA]], has been found to produce long-lasting [[serotonergic]] [[neurotoxicity]] in rats, and the same could also prove true for 5-chloro-αMT and other monoamine-releasing tryptamines.<ref name="pmid1722753">{{cite journal | author = Huang XM, Johnson MP, Nichols DE | title = Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase) | journal = European Journal of Pharmacology | volume = 200 | issue = 1 | pages = 187–90 |date=July 1991 | pmid = 1722753 | doi = 10.1016/0014-2999(91)90686-K| url = }}</ref>
A related agent, [[5-fluoro-α-methyltryptamine]] (5-fluoro-αMT), also known as PAL-544, is a potent [[MAO-A inhibitor]] in addition to SNDRA and 5-HT<sub>2A</sub> receptor agonist.<ref name="pmid24796848" /><ref name="pmid3797802">{{cite journal | author = Kinemuchi H, Arai Y | title = Selective inhibition of monoamine oxidase A and B by two substrate-analogues, 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methylphenethylamine | journal = Res. Commun. Chem. Pathol. Pharmacol. | volume = 54 | issue = 1 | pages = 125–8 |date=October 1986 | pmid = 3797802 | doi = | url = }}</ref><ref name="pmid25193229" /> Due to their close [[chemical structure|structural]] similarity, 5-chloro-αMT might also possess activity as an MAO-A inhibitor, a property which, in combination with its activity as [[monoamine releasing agent]], could potentially render it dangerous in an analogous manner to the [[substituted phenethylamine|phenethylamine]] derivative [[para-Methoxyamphetamine|''para''-methoxyamphetamine]] (PMA).<ref name="pmid11041537">{{cite journal | author = Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F | title = Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat | journal = Progress in Neuro-psychopharmacology & Biological Psychiatry | volume = 24 | issue = 6 | pages = 955–77 |date=August 2000 | pmid = 11041537 | doi = 10.1016/S0278-5846(00)00113-5| url = http://linkinghub.elsevier.com/retrieve/pii/S0278-5846(00)00113-5}}</ref> In addition, [[α-ethyltryptamine]] (αET), an SNDRA and close [[structural analogue]] of αMT and 5-chloro-αMT, like many other [[releasing agent]]s of both 5-HT and DA such as [[3,4-methylenedioxy-N-methylamphetamine|MDMA]], has been found to produce long-lasting [[serotonergic]] [[neurotoxicity]] in rats, and the same could also prove true for 5-chloro-αMT and other monoamine-releasing tryptamines.<ref name="pmid1722753">{{cite journal | author = Huang XM, Johnson MP, Nichols DE | title = Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase) | journal = European Journal of Pharmacology | volume = 200 | issue = 1 | pages = 187–90 |date=July 1991 | pmid = 1722753 | doi = 10.1016/0014-2999(91)90686-K| url = }}</ref>


As a 5-HT<sub>2A</sub> receptor agonist, 5-chloro-αMT likely possesses the capacity for [[psychedelic drug|psychedelic]] effects.<ref name="pmid25193229" /><ref name="pmid6258178">{{cite journal | author = Yamamoto T, Ueki S | title = The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs | journal = Pharmacol. Biochem. Behav. | volume = 14 | issue = 1 | pages = 89–95 |date=January 1981 | pmid = 6258178 | doi = 10.1016/0091-3057(81)90108-8| url = }}</ref> Indeed, its close analog 5-fluoro-αMT produces a strong [[head-twitch response]] in rats,<ref name="pmid9535013">{{cite journal | author = Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y | title = Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice | journal = Br. J. Pharmacol. | volume = 123 | issue = 5 | pages = 855–62 |date=March 1998 | pmid = 9535013 | pmc = 1565246 | doi = 10.1038/sj.bjp.0701695 | url = http://dx.doi.org/10.1038/sj.bjp.0701695}}</ref> a property which is highly correlated with psychedelic effects in humans.<ref name="pmid5302272">{{cite journal | author = Corne SJ, Pickering RW | title = A possible correlation between drug-induced hallucinations in man and a behavioural response in mice | journal = Psychopharmacologia | volume = 11 | issue = 1 | pages = 65–78 | year = 1967 | pmid = 5302272 | doi = 10.1007/bf00401509| url = }}</ref><ref name="pmid6258178" />
As a 5-HT<sub>2A</sub> receptor agonist, 5-chloro-αMT very likely possesses the capacity for [[psychedelic drug|psychedelic]] effects.<ref name="pmid25193229" /><ref name="pmid6258178">{{cite journal | author = Yamamoto T, Ueki S | title = The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs | journal = Pharmacol. Biochem. Behav. | volume = 14 | issue = 1 | pages = 89–95 |date=January 1981 | pmid = 6258178 | doi = 10.1016/0091-3057(81)90108-8| url = }}</ref> Indeed, its close analog 5-fluoro-αMT produces a strong [[head-twitch response]] in rats,<ref name="pmid9535013">{{cite journal | author = Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y | title = Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice | journal = Br. J. Pharmacol. | volume = 123 | issue = 5 | pages = 855–62 |date=March 1998 | pmid = 9535013 | pmc = 1565246 | doi = 10.1038/sj.bjp.0701695 | url = http://dx.doi.org/10.1038/sj.bjp.0701695}}</ref> a property which is highly correlated with psychedelic effects in humans,<ref name="pmid5302272">{{cite journal | author = Corne SJ, Pickering RW | title = A possible correlation between drug-induced hallucinations in man and a behavioural response in mice | journal = Psychopharmacologia | volume = 11 | issue = 1 | pages = 65–78 | year = 1967 | pmid = 5302272 | doi = 10.1007/bf00401509| url = }}</ref><ref name="pmid6258178" /> and αMT is well-established as a psychedelic drug in humans.<ref name="AraújoCarvalho2015">{{cite journal|last1=Araújo|first1=Ana Margarida|last2=Carvalho|first2=Félix|last3=Bastos|first3=Maria de Lourdes|last4=Guedes de Pinho|first4=Paula|last5=Carvalho|first5=Márcia|title=The hallucinogenic world of tryptamines: an updated review|journal=Archives of Toxicology|volume=89|issue=8|year=2015|pages=1151–1173|issn=0340-5761|doi=10.1007/s00204-015-1513-x}}</ref>


==See also==
==See also==

Revision as of 22:27, 26 January 2016

5-Chloro-αMT
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
  • 1-(5-Chloro-1H-indol-3-yl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H13ClN2
Molar mass208.687 g/mol g·mol−1
3D model (JSmol)
  • CC(Cc1c[nH]c2c1cc(cc2)Cl)N
  • InChI=1S/C11H13ClN2/c1-7(13)4-8-6-14-11-3-2-9(12)5-10(8)11/h2-3,5-7,14H,4,13H2,1H3
  • Key:QMKOQSCXSYPIPB-UHFFFAOYSA-N

5-Chloro-α-methyltryptamine (5-Chloro-αMT), also known as PAL-542, is a tryptamine derivative related to α-methyltryptamine (αMT) and one of only a few known specific serotonin-dopamine releasing agents (SDRAs).[1][2] It has been investigated in animals as a potential treatment for cocaine dependence.[2] The EC50 values of 5-chloro-αMT in evoking the in vitro release of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in rat synaptosomes were reported as 16 nM, 54 nM, and 3434 nM, with an NE/DA ratio of 63.6 and a DA/5-HT ratio of 3.38, indicating that it is a highly specific and well-balanced SDRA.[2] However, 5-chloro-αMT has also been found to act as a potent full agonist of the 5-HT2A receptor, with an EC50 value of 6.27 nM and an efficacy of 105%, and almost assuredly acts as a potent agonist of other serotonin receptors as well.[1]

5-Chloro-αMT was found to not reliably produce intracranial self-administration in rats or substitute for cocaine in rats or monkeys.[2] It was found through study of 5-chloro-αMT in rhesus monkeys that norepinephrine release has minimal influence on the abuse potential of monoamine releasing agents and that loss of norepinephrine release activity does not affect efficacy in reducing cocaine self-administration in SDRAs relative to serotonin-norepinephrine-dopamine releasing agents (SNDRAs) such as naphthylisopropylamine (PAL-287).[2] However, SDRAs like PAL-542 would, in theory, be expected to produce fewer side effects (including sympathomimetic/cardiovascular effects, insomnia, hyperthermia, and anxiety) relative to SNDRAs, and thus would likely be comparatively more favorable in the treatment of cocaine dependence and other conditions.[2]

A related agent, 5-fluoro-α-methyltryptamine (5-fluoro-αMT), also known as PAL-544, is a potent MAO-A inhibitor in addition to SNDRA and 5-HT2A receptor agonist.[2][3][1] Due to their close structural similarity, 5-chloro-αMT might also possess activity as an MAO-A inhibitor, a property which, in combination with its activity as monoamine releasing agent, could potentially render it dangerous in an analogous manner to the phenethylamine derivative para-methoxyamphetamine (PMA).[4] In addition, α-ethyltryptamine (αET), an SNDRA and close structural analogue of αMT and 5-chloro-αMT, like many other releasing agents of both 5-HT and DA such as MDMA, has been found to produce long-lasting serotonergic neurotoxicity in rats, and the same could also prove true for 5-chloro-αMT and other monoamine-releasing tryptamines.[5]

As a 5-HT2A receptor agonist, 5-chloro-αMT very likely possesses the capacity for psychedelic effects.[1][6] Indeed, its close analog 5-fluoro-αMT produces a strong head-twitch response in rats,[7] a property which is highly correlated with psychedelic effects in humans,[8][6] and αMT is well-established as a psychedelic drug in humans.[9]

See also

References

  1. ^ a b c d Blough BE, Landavazo A, Partilla JS; et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–8. doi:10.1016/j.bmcl.2014.07.062. PMID 25193229.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b c d e f g Banks ML, Bauer CT, Blough BE; et al. (June 2014). "Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys". Exp Clin Psychopharmacol. 22 (3): 274–84. doi:10.1037/a0036595. PMID 24796848.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Kinemuchi H, Arai Y (October 1986). "Selective inhibition of monoamine oxidase A and B by two substrate-analogues, 5-fluoro-alpha-methyltryptamine and p-chloro-beta-methylphenethylamine". Res. Commun. Chem. Pathol. Pharmacol. 54 (1): 125–8. PMID 3797802.
  4. ^ Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F (August 2000). "Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat". Progress in Neuro-psychopharmacology & Biological Psychiatry. 24 (6): 955–77. doi:10.1016/S0278-5846(00)00113-5. PMID 11041537.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Huang XM, Johnson MP, Nichols DE (July 1991). "Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase)". European Journal of Pharmacology. 200 (1): 187–90. doi:10.1016/0014-2999(91)90686-K. PMID 1722753.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ a b Yamamoto T, Ueki S (January 1981). "The role of central serotonergic mechanisms on head-twitch and backward locomotion induced by hallucinogenic drugs". Pharmacol. Biochem. Behav. 14 (1): 89–95. doi:10.1016/0091-3057(81)90108-8. PMID 6258178.
  7. ^ Chairungsrilerd N, Furukawa K, Tadano T, Kisara K, Ohizumi Y (March 1998). "Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of mice". Br. J. Pharmacol. 123 (5): 855–62. doi:10.1038/sj.bjp.0701695. PMC 1565246. PMID 9535013.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Corne SJ, Pickering RW (1967). "A possible correlation between drug-induced hallucinations in man and a behavioural response in mice". Psychopharmacologia. 11 (1): 65–78. doi:10.1007/bf00401509. PMID 5302272.
  9. ^ Araújo, Ana Margarida; Carvalho, Félix; Bastos, Maria de Lourdes; Guedes de Pinho, Paula; Carvalho, Márcia (2015). "The hallucinogenic world of tryptamines: an updated review". Archives of Toxicology. 89 (8): 1151–1173. doi:10.1007/s00204-015-1513-x. ISSN 0340-5761.


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