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m added a "likely" to the unsubstantiated claim that Cyclazodone is a TAAR1 agonist
 
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{{SummarySheet}}
{{SummarySheet}}
{{SubstanceBox/Cyclazodone}}
{{SubstanceBox/Cyclazodone}}
'''N-Cyclopropylpemoline''' (also known as '''Cyclazodone''') is a novel [[psychoactive class::stimulant]] substance of the [[chemical class::4-oxazolidinone]] class. It is structurally related to [[pemoline]] and [[4-methylaminorex]]. The mechanism of action involves promoting the release of [[dopamine]] and [[norepinephrine]] in the brain.


'''N-Cyclopropylpemoline''' (also known as '''Cyclazodone''') is a novel [[psychoactive class::stimulant]] substance of the [[chemical class::4-oxazolidinone]] class that produces [[stimulating]] and [[focus enhancement|focus enhancing]] effects when [[administered]]. It is structurally related to [[pemoline]] and [[4-methylaminorex]].
Cyclazodone was developed in the 1960s by the American Cyanamid Company. Its non-clinical use has only found recent attention as a [[research chemical]] study aid. It should be noted that the lack of pharmacological data and extremely limited history of human usage pose considerable concern regarding its long-term use as a substitute for prescription stimulants.
 
[[Subjective effects]] include [[stimulation]], [[focus enhancement]], [[stamina enhancement]], [[increased blood pressure]], and mild [[euphoria]]. Some anecdotal reports suggest that [[cyclazodone]] and its parent compound [[pemoline]] may have nootropic properties similar to central nervous system stimulants such as [[methylphenidate]] and [[amphetamine]].


Cyclazodone was developed in the 1960s by the American Cyanamid Company. Its non-clinical use has only found recent attention as a [[research chemical]] study aid. It should be noted that the lack of pharmacological data and extremely limited history of human usage pose considerable concern regarding its long-term use as a substitute for prescription stimulants.
Cyclazodone had no documented history of recreational human usage prior to its appearance on the online research chemical market in 2017. Considering similar compounds, it is speculated that it may possess hepatotoxic and other yet-to-be-discovered toxic properties.  


Cyclazodone has no documented history of recreational human usage before it appeared on the online research chemical market in 2017. Based on related compounds, it is speculated that it likely possesses hepatotoxic and other not-yet-known toxic properties. It is strongly advised to use [[responsible drug use|harm reduction practices]] if using this substance.
It is strongly advised to use [[responsible drug use|harm reduction practices]] if using this substance.


==Chemistry==
==Chemistry==
Cyclazodone is a phenyl 4-oxazolidinone that differs from the parent [[pemoline]] by an N-cyclopropyl group. Compounds like cyclazodone of the 4-oxazolidinone class can be considered as 4-oxy derivatives of the 2-amino-5-aryloxazoline class including [[aminorex]], [[fluminorex]], and [[4-methylaminorex]], conformationally restricted analogues of [[phenethylamines]] and [[amphetamines]]. Cyclazodone is structurally most closely related, not to pemoline, but rather to two N-substituted derivatives of pemoline — [[fenozolone]] (N-ethyl pemoline) and [[thozalinone]] (N,N-dimethyl pemoline).
Cyclazodone is a phenyl 4-oxazolidinone that differs from the parent [[pemoline]] by an N-cyclopropyl group. Compounds like cyclazodone of the 4-oxazolidinone class can be considered as 4-oxy derivatives of the 2-amino-5-aryloxazoline class including [[aminorex]], [[fluminorex]], and [[4-methylaminorex]], conformationally restricted analogues of [[phenethylamines]] and [[amphetamines]].
 
Cyclazodone is structurally most closely related, not to pemoline, but rather to two N-substituted derivatives of pemoline — [[fenozolone]] (N-ethyl pemoline) and [[thozalinone]] (N,N-dimethyl pemoline).


==Pharmacology==
==Pharmacology==
Cyclazodone is an approximately 3x - 5x more potent N-cyclopropyl derivative of [[pemoline]]. Pemoline is considered to be [[dopamine|dopaminergic]], but its precise method of action has not been fully determined.<ref>"Cylert (Pemoline)" (PDF). FDA. December 2002.</ref> Pemoline has minimal affinity for [[noradrenaline]] receptors and thus has minimal sympathomimetic side effects compared with typical dopaminergic central nervous system stimulants such as methylphenidate and [[Isomer|dextro]]-amphetamine.
Cyclazodone is an approximately 3x - 5x more potent N-cyclopropyl derivative of [[pemoline]]. Pemoline is considered to be [[dopamine|dopaminergic]], but its precise method of action has not been fully determined.<ref>"Cylert (Pemoline)" (PDF). FDA. December 2002.</ref> Pemoline has minimal affinity for [[noradrenaline]] receptors and thus has minimal sympathomimetic side effects compared with typical dopaminergic central nervous system stimulants such as methylphenidate and [[Isomer|dextro]]-amphetamine.


According to patents filed by the inventors, cyclazodone exhibited central nervous system stimulating properties and anorexigenic properties much more potent than those of pemoline, and more potent than those of various other N-lower-alkyl-substituted pemoline derivatives. At the time cyclazodone also offered a much more favorable therapeutic index and margin of safety than pemoline and other N-lower-alkyl-substituted pemoline derivatives.<ref>Val De Marne, Don Pierre R. L. Guidicelli, and Henry Najer. 5-Phenyl-2-Cyclopropylamino-4-Oxazolidinone. Les Laboratoires Dausse, assignee. Patent US3609159. 28 Sept. 1971.</ref>
According to patents filed by the inventors, cyclazodone exhibited central nervous system stimulating properties and anorexigenic properties more potent than that of pemoline and various other N-lower-alkyl-substituted pemoline derivatives. At the time cyclazodone also offered a much more favorable therapeutic index and margin of safety than pemoline and other N-lower-alkyl-substituted pemoline derivatives.<ref name="GuidicelliPatent">{{Citation | vauthors=((Guidicelli, D. P. R. L.)), ((Najer, H.)) | title=5-phenyl-2-cyclopropylamino-4-oxazolinone, and process for making the same | url=https://patents.google.com/patent/US3609159A/en}}</ref>


In animal models, cyclazodone exhibits central nervous system stimulant and antidepressant efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine. The duration of maximum activity spanned 180 minutes, and the total duration of excitation was in excess of 6 hours.<ref>Val De Marne, Don Pierre R. L. Guidicelli, and Henry Najer. 5-Phenyl-2-Cyclopropylamino-4-Oxazolidinone. Les Laboratoires Dausse, assignee. Patent US3609159. 28 Sept. 1971.</ref> Furthermore, according to the inventor's patents, cyclazodone also possessed anorexic efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine in animal models, yet the toxicity of cyclazodone was found to be low in comparison with the activity thereof.<ref>Val De Marne, Don Pierre R. L. Guidicelli, and Henry Najer. 5-Phenyl-2-Cyclopropylamino-4-Oxazolidinone. Les Laboratoires Dausse, assignee. Patent GB1005738A. 29 Sept. 1965.</ref>
In animal models, cyclazodone exhibits central nervous system stimulant and antidepressant efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine. The duration of maximum activity spanned 180 minutes, and the total duration of excitation was in excess of 6 hours.<ref name="GuidicelliPatent" /> Furthermore, according to the inventor's patents, cyclazodone also possessed anorexic efficacy and potency at least equal to that of [[Isomer|dextro]]-amphetamine in animal models, yet the toxicity of cyclazodone was found to be low in comparison with the activity thereof.<ref name="GuidicelliPatent" />


===Pharmacodynamics===
===Pharmacodynamics===
Cyclazodone is an [[amphetamine]]-like [[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>The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005101/</ref><ref>Drug banks amphetamine targets | 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.
Cyclazodone is likely an [[amphetamine]]-like [[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=Amphetamine | url=https://go.drugbank.com/drugs#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.


==Subjective effects==
==Subjective effects==
The effects of cyclazodone have been compared to those of [[amphetamine]], but with the addition of a low to moderate affinity for [[serotonin]] release comparable to that of [[methamphetamine]] and [[3-FMA]].
The stimulant effects of cyclazodone have been compared to those of [[amphetamine]], but with the addition of a low to moderate affinity for [[serotonin]] release comparable to that of [[methamphetamine]] and [[3-FMA]]. Additionally, it is noticeably less euphoric than amphetamine and appears to have less sympathomimetic activation.
 
Some anecdotal reports suggest that [[cyclazodone]] and its parent compound [[pemoline]] may have nootropic properties similar to central nervous system stimulants such as [[methylphenidate]] and [[amphetamine]].


{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
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The toxicity and long-term health effects of recreational cyclazodone use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because cyclazodone has a very limited history of human usage.
The toxicity and long-term health effects of recreational cyclazodone use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because cyclazodone has a very limited history of human usage.


Another compound related in structure, [[4-methylaminorex]], is associated with pulmonary hypertension<ref>https://www.ncbi.nlm.nih.gov/pubmed/11083709</ref>; though, it is reported to induce far stronger stimulation than that of cyclazodone.
Another compound related in structure, [[4-methylaminorex]], is associated with pulmonary hypertension<ref>{{cite journal | vauthors=((Gaine, S. P.)), ((Rubin, L. J.)), ((Kmetzo, J. J.)), ((Palevsky, H. I.)), ((Traill, T. A.)) | journal=Chest | title=Recreational use of aminorex and pulmonary hypertension | volume=118 | issue=5 | pages=1496–1497 | date= November 2000 | issn=0012-3692 | doi=10.1378/chest.118.5.1496}}</ref>; though, it is reported to induce far stronger stimulation than that of cyclazodone.


The structurally related compound pemoline was removed from the market after it was found to cause liver damage in children.<ref>Marotta, P. J., & Roberts, E. A. (1998). Pemoline hepatotoxicity in children. The Journal of Pediatrics, 132(5), 894-897.</ref>
The structurally related compound pemoline was removed from the market after it was found to cause liver damage in children.<ref>{{cite journal | vauthors=((Marotta, P. J.)), ((Roberts, E. A.)) | journal=The Journal of Pediatrics | title=Pemoline hepatotoxicity in children | volume=132 | issue=5 | pages=894–897 | date= May 1998 | url=https://linkinghub.elsevier.com/retrieve/pii/S0022347698703294 | issn=00223476 | doi=10.1016/S0022-3476(98)70329-4}}</ref>


In rodents and primates, sufficiently high doses of monoamine [[releasing agent|releasing agents]] cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by reduced transporter and receptor function. There is no evidence that [[releasing agent]]s are directly neurotoxic in humans. However, large doses of [[releasing agent]]s may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.{{citation needed}}
In rodents and primates, sufficiently high doses of monoamine [[releasing agent|releasing agents]] cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by reduced transporter and receptor function. There is no evidence that [[releasing agent]]s are directly neurotoxic in humans. However, large doses of [[releasing agent]]s may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.{{citation needed}}
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===Psychosis===
===Psychosis===
{{Main|Stimulant psychosis}}
{{Main|Stimulant psychosis}}
Based on its pharmacological similarity to other stimulants, it is likely that misuse of this compound can result in state of psychosis marked by a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], or [[Delusions|delusions]]).<ref>http://www.drugabuse.gov/drugs-abuse/emerging-trends</ref><ref name="amppsychosis">Shoptaw, S. J., Kao, U., & Ling, W. (2009). Treatment for amphetamine psychosis. The Cochrane Library.</ref> A review on the treatment for [[amphetamine]] and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="amppsychosis" /><ref>Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570.</ref> The same review asserts that based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="amppsychosis" /> Psychosis very rarely arises from therapeutic use. The combination of the prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.{{citation needed}}
Based on its pharmacological similarity to other stimulants, it is likely that misuse of this compound can result in state of psychosis marked by a variety of symptoms (e.g., [[Paranoia|paranoia]], [[External hallucinations|hallucinations]], or [[Delusions|delusions]]).<ref>{{Citation | vauthors=((National Institute on Drug Abuse)) | title=Emerging Trends | url=https://nida.nih.gov/research-topics/emerging-trends-alerts}}</ref><ref name="amppsychosis">{{cite book | vauthors=((Shoptaw, S. J.)), ((Kao, U.)), ((Ling, W. W.)) | veditors=((The Cochrane Collaboration)) | date=8 October 2008 | chapter=The Cochrane Database of Systematic Reviews (Complete Reviews) | title=Treatment for amphetamine psychosis | publisher=John Wiley & Sons, Ltd | pages=CD003026.pub2 | url=https://doi.wiley.com/10.1002/14651858.CD003026.pub2 | doi=10.1002/14651858.CD003026.pub2}}</ref> A review on the treatment for [[amphetamine]] and [[methamphetamine]] abuse-induced psychosis states that about 5–15% of users fail to recover completely.<ref name="amppsychosis" /><ref>{{cite book | vauthors=((Hofmann, F. G.)) | date= 1983 | title=A handbook on drug and alcohol abuse: the biomedical aspects | publisher=Oxford University Press | edition=2nd ed | isbn=9780195030563}}</ref> The same review asserts that based upon at least one trial, [[antipsychotic]] medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="amppsychosis" /> Psychosis very rarely arises from therapeutic use. The combination of the prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.{{citation needed}}


===Dangerous interactions===
===Dangerous interactions===
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*'''Germany''': Cyclazodone is not a controlled substance under the BtMG (''Narcotics Act'')<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/BJNR106810981.html|title=Gesetz über den Verkehr mit Betäubungsmitteln (Betäubungsmittelgesetz - BtMG)|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> or the NpSG (''New Psychoactive Substances Act'').<ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/BJNR261510016.html|title=Neue-psychoaktive-Stoffe-Gesetz (NpSG)|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> According to §2 AMG (''Medicines Act'') it would fall under the definition of a medicine because it induces pharmacological effect.<ref>{{cite web|url=https://www.gesetze-im-internet.de/amg_1976/__2.html|title=§ 2 AMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> By a decision of the European Court of Justice, this definition was declared ineffective because it was not compatible with EU law.<ref>{{cite news|url=https://www.lto.de/recht/hintergruende/h/eugh-urteil-c35813-c18114-legal-highs-kein-arzneimittel-strafbar-amg-btmg/|title= Cannabinoide Kräutermischungen vor dem EuGH: Legal Highs bleiben legal|publisher=LTO|author=Prof. Dr. Helmut Pollähne|trans-title=Cannabinoid herbal mixtures at the ECJ: Legal highs stay legal|date=July 11, 2014|access-date=December 28, 2019|language=de}}</ref> Cyclazodone can be considered legal.
*'''Germany''': Cyclazodone is not a controlled substance under the BtMG (''Narcotics Act'')<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/BJNR106810981.html|title=Gesetz über den Verkehr mit Betäubungsmitteln (Betäubungsmittelgesetz - BtMG)|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> or the NpSG (''New Psychoactive Substances Act'').<ref>{{cite web|url=https://www.gesetze-im-internet.de/npsg/BJNR261510016.html|title=Neue-psychoaktive-Stoffe-Gesetz (NpSG)|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> According to §2 AMG (''Medicines Act'') it would fall under the definition of a medicine because it induces pharmacological effect.<ref>{{cite web|url=https://www.gesetze-im-internet.de/amg_1976/__2.html|title=§ 2 AMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 28, 2019|language=de}}</ref> By a decision of the European Court of Justice, this definition was declared ineffective because it was not compatible with EU law.<ref>{{cite news|url=https://www.lto.de/recht/hintergruende/h/eugh-urteil-c35813-c18114-legal-highs-kein-arzneimittel-strafbar-amg-btmg/|title= Cannabinoide Kräutermischungen vor dem EuGH: Legal Highs bleiben legal|publisher=LTO|author=Prof. Dr. Helmut Pollähne|trans-title=Cannabinoid herbal mixtures at the ECJ: Legal highs stay legal|date=July 11, 2014|access-date=December 28, 2019|language=de}}</ref> Cyclazodone can be considered legal.
* '''United States''': Cyclazodone being an analogue of [[pemoline]], a Schedule IV controlled substance in the US, may fall under Federal Analogue Act, 21 U.S.C. § 813<ref>https://www.law.cornell.edu/uscode/text/21/813</ref> when intended for human consumption.
*'''Switzerland''': Cyclazodone is not controlled under Buchstabe A, B, C and D. It could be considered legal.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''United States''': Cyclazodone being an analogue of [[pemoline]], a Schedule IV controlled substance in the US, may fall under Federal Analogue Act, 21 U.S.C. § 813<ref>{{Citation | title=21 U.S. Code § 813 - Treatment of controlled substance analogues | url=https://www.law.cornell.edu/uscode/text/21/813}}</ref> when intended for human consumption.


==See also==
==See also==
*[[Responsible use]]
*[[Responsible use]]
*[[Research chemicals]]
*[[Research chemicals]]
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==External links==
==External links==
*[https://en.wikipedia.org/wiki/Cyclazodone Cyclazodone (Wikipedia)]
*[https://en.wikipedia.org/wiki/Cyclazodone Cyclazodone (Wikipedia)]
*[https://isomerdesign.com/PiHKAL/explore.php?id=1434 Cyclazodone (Isomer Design)]
*[https://isomerdesign.com/PiHKAL/explore.php?id=1434 Cyclazodone (Isomer Design)]


==Literature==
==Literature==
* Segal, D. S., Cox Jr, R. H., Stern, W. C., & Maickel, R. P. (1967). Stimulatory effects of pemoline and cyclopropylpemoline on continuous avoidance behavior: similarity to effects of D-amphetamine. Life Sciences, 6(23), 2567-2572. https://doi.org/10.1016/0024-3205(67)90322-0
 
*Segal, D. S., Cox Jr, R. H., Stern, W. C., & Maickel, R. P. (1967). Stimulatory effects of pemoline and cyclopropylpemoline on continuous avoidance behavior: similarity to effects of D-amphetamine. Life Sciences, 6(23), 2567-2572. https://doi.org/10.1016/0024-3205(67)90322-0


==References==
==References==
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[[Category:Aminorex]]
[[Category:Aminorex]]
[[Category:Research chemical]]
[[Category:Research chemical]]
[[Category:Proofread]]
[[Category:Approval]]

Latest revision as of 16:54, 31 March 2024

Summary sheet: Cyclazodone
Cyclazodone
Chemical Nomenclature
Common names Cyclazodone
Substitutive name N-Cyclopropylpemoline
Systematic name 2-(Cyclopropylamino)-5-phenyl-1,3-oxazol-4-one
Class Membership
Psychoactive class Stimulant
Chemical class Aminorex
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold 5 mg
Light 5 - 15 mg
Common 15 - 25 mg
Strong 25 - 60 mg
Heavy 60 mg + Liver damage may result from heavy or sustained usage.
Duration
Total 5 - 7 hours
Onset 20 - 45 minutes









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Interactions

N-Cyclopropylpemoline (also known as Cyclazodone) is a novel stimulant substance of the 4-oxazolidinone class. It is structurally related to pemoline and 4-methylaminorex. The mechanism of action involves promoting the release of dopamine and norepinephrine in the brain.

Cyclazodone was developed in the 1960s by the American Cyanamid Company. Its non-clinical use has only found recent attention as a research chemical study aid. It should be noted that the lack of pharmacological data and extremely limited history of human usage pose considerable concern regarding its long-term use as a substitute for prescription stimulants.

Subjective effects include stimulation, focus enhancement, stamina enhancement, increased blood pressure, and mild euphoria. Some anecdotal reports suggest that cyclazodone and its parent compound pemoline may have nootropic properties similar to central nervous system stimulants such as methylphenidate and amphetamine.

Cyclazodone had no documented history of recreational human usage prior to its appearance on the online research chemical market in 2017. Considering similar compounds, it is speculated that it may possess hepatotoxic and other yet-to-be-discovered toxic properties.

It is strongly advised to use harm reduction practices if using this substance.

Chemistry

Cyclazodone is a phenyl 4-oxazolidinone that differs from the parent pemoline by an N-cyclopropyl group. Compounds like cyclazodone of the 4-oxazolidinone class can be considered as 4-oxy derivatives of the 2-amino-5-aryloxazoline class including aminorex, fluminorex, and 4-methylaminorex, conformationally restricted analogues of phenethylamines and amphetamines.

Cyclazodone is structurally most closely related, not to pemoline, but rather to two N-substituted derivatives of pemoline — fenozolone (N-ethyl pemoline) and thozalinone (N,N-dimethyl pemoline).

Pharmacology

Cyclazodone is an approximately 3x - 5x more potent N-cyclopropyl derivative of pemoline. Pemoline is considered to be dopaminergic, but its precise method of action has not been fully determined.[1] Pemoline has minimal affinity for noradrenaline receptors and thus has minimal sympathomimetic side effects compared with typical dopaminergic central nervous system stimulants such as methylphenidate and dextro-amphetamine.

According to patents filed by the inventors, cyclazodone exhibited central nervous system stimulating properties and anorexigenic properties more potent than that of pemoline and various other N-lower-alkyl-substituted pemoline derivatives. At the time cyclazodone also offered a much more favorable therapeutic index and margin of safety than pemoline and other N-lower-alkyl-substituted pemoline derivatives.[2]

In animal models, cyclazodone exhibits central nervous system stimulant and antidepressant efficacy and potency at least equal to that of dextro-amphetamine. The duration of maximum activity spanned 180 minutes, and the total duration of excitation was in excess of 6 hours.[2] Furthermore, according to the inventor's patents, cyclazodone also possessed anorexic efficacy and potency at least equal to that of dextro-amphetamine in animal models, yet the toxicity of cyclazodone was found to be low in comparison with the activity thereof.[2]

Pharmacodynamics

Cyclazodone is likely an amphetamine-like 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.[3][4][5] 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 cognitive and physical stimulation within the user.

Subjective effects

The stimulant effects of cyclazodone have been compared to those of amphetamine, but with the addition of a low to moderate affinity for serotonin release comparable to that of methamphetamine and 3-FMA. Additionally, it is noticeably less euphoric than amphetamine and appears to have less sympathomimetic activation.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects

Visual effects

Cognitive effects

After effects

Experience reports

There are currently 0 experience reports which describe the effects of this substance in our experience index.


Toxicity and harm potential

The toxicity and long-term health effects of recreational cyclazodone use do not seem to have been studied in any scientific context and the exact toxic dosage is unknown. This is because cyclazodone has a very limited history of human usage.

Another compound related in structure, 4-methylaminorex, is associated with pulmonary hypertension[6]; though, it is reported to induce far stronger stimulation than that of cyclazodone.

The structurally related compound pemoline was removed from the market after it was found to cause liver damage in children.[7]

In rodents and primates, sufficiently high doses of monoamine releasing agents cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by reduced transporter and receptor function. There is no evidence that releasing agents are directly neurotoxic in humans. However, large doses of releasing agents may cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.[citation needed]

It is strongly recommended that one use harm reduction practices when using this substance.

Tolerance and addiction potential

Addiction is a serious risk with heavy recreational stimulant use but is unlikely to arise from typical long-term medical use at therapeutic doses. Notably, the structurally related compound pemoline fails to demonstrate a potential for self-administration in primates and is considered to have reduced risk of dependence relative to those more typical dopaminergic stimulants. Caution is nonetheless advised, as with other monoamine releasing agents.

Tolerance to many of the effects of cyclazodone develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Cyclazodone presents cross-tolerance with [[Cross-tolerance::all dopaminergic stimulants]], meaning that after the consumption of cyclazodone all stimulants will have a reduced effect.

Psychosis

Main article: Stimulant psychosis

Based on its pharmacological similarity to other stimulants, it is likely that misuse of this compound can result in state of psychosis marked by a variety of symptoms (e.g., paranoia, hallucinations, or delusions).[8][9] A review on the treatment for amphetamine and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.[9][10] The same review asserts that based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[9] Psychosis very rarely arises from therapeutic use. The combination of the prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.[citation needed]

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

  • "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] & "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - 25x compounds are highly stimulating and physically straining. Combinations with Cyclazodone should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
  • "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
  • "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
  • "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
  • "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
  • "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
  • "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Cyclazodone may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
  • "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Tramadol is known to lower the seizure threshold[11] and combinations with stimulants may further increase this risk.

Cyclazodone is currently a gray area compound within all parts of the world, meaning its regulation lies in a legal gray area and that it is not known to be specifically illegal ("scheduled") within any country. However, people may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume. It is a banned stimulant under the World Anti-Doping Agency prohibited list.

  • Germany: Cyclazodone is not a controlled substance under the BtMG (Narcotics Act)[12] or the NpSG (New Psychoactive Substances Act).[13] According to §2 AMG (Medicines Act) it would fall under the definition of a medicine because it induces pharmacological effect.[14] By a decision of the European Court of Justice, this definition was declared ineffective because it was not compatible with EU law.[15] Cyclazodone can be considered legal.
  • Switzerland: Cyclazodone is not controlled under Buchstabe A, B, C and D. It could be considered legal.[16]
  • United States: Cyclazodone being an analogue of pemoline, a Schedule IV controlled substance in the US, may fall under Federal Analogue Act, 21 U.S.C. § 813[17] when intended for human consumption.

See also

Literature

  • Segal, D. S., Cox Jr, R. H., Stern, W. C., & Maickel, R. P. (1967). Stimulatory effects of pemoline and cyclopropylpemoline on continuous avoidance behavior: similarity to effects of D-amphetamine. Life Sciences, 6(23), 2567-2572. https://doi.org/10.1016/0024-3205(67)90322-0

References

  1. "Cylert (Pemoline)" (PDF). FDA. December 2002.
  2. 2.0 2.1 2.2 Guidicelli, D. P. R. L., Najer, H., 5-phenyl-2-cyclopropylamino-4-oxazolinone, and process for making the same 
  3. Miller, G. M. (January 2011). "The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity". Journal of neurochemistry. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. ISSN 0022-3042. 
  4. Amphetamine 
  5. TA1 receptor | http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=364
  6. Gaine, S. P., Rubin, L. J., Kmetzo, J. J., Palevsky, H. I., Traill, T. A. (November 2000). "Recreational use of aminorex and pulmonary hypertension". Chest. 118 (5): 1496–1497. doi:10.1378/chest.118.5.1496. ISSN 0012-3692. 
  7. Marotta, P. J., Roberts, E. A. (May 1998). "Pemoline hepatotoxicity in children". The Journal of Pediatrics. 132 (5): 894–897. doi:10.1016/S0022-3476(98)70329-4. ISSN 0022-3476. 
  8. National Institute on Drug Abuse, Emerging Trends 
  9. 9.0 9.1 9.2 Shoptaw, S. J., Kao, U., Ling, W. W. (8 October 2008). "The Cochrane Database of Systematic Reviews (Complete Reviews)". In The Cochrane Collaboration. Treatment for amphetamine psychosis. John Wiley & Sons, Ltd. pp. CD003026.pub2. doi:10.1002/14651858.CD003026.pub2. 
  10. Hofmann, F. G. (1983). A handbook on drug and alcohol abuse: the biomedical aspects (2nd ed ed.). Oxford University Press. ISBN 9780195030563. 
  11. Talaie, H.; Panahandeh, R.; Fayaznouri, M. R.; Asadi, Z.; Abdollahi, M. (2009). "Dose-independent occurrence of seizure with tramadol". Journal of Medical Toxicology. 5 (2): 63–67. doi:10.1007/BF03161089. eISSN 1937-6995. ISSN 1556-9039. OCLC 163567183. 
  12. "Gesetz über den Verkehr mit Betäubungsmitteln (Betäubungsmittelgesetz - BtMG)" (in Deutsch). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 28, 2019. 
  13. "Neue-psychoaktive-Stoffe-Gesetz (NpSG)" (in Deutsch). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 28, 2019. 
  14. "§ 2 AMG" (in Deutsch). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 28, 2019. 
  15. Prof. Dr. Helmut Pollähne (July 11, 2014). "Cannabinoide Kräutermischungen vor dem EuGH: Legal Highs bleiben legal" [Cannabinoid herbal mixtures at the ECJ: Legal highs stay legal] (in Deutsch). LTO. Retrieved December 28, 2019. 
  16. "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in Deutsch). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020. 
  17. 21 U.S. Code § 813 - Treatment of controlled substance analogues