VCU-1012

VCU 1012

VCU-1012

VCU-1012
Clinical data
Other namesVCU1012; 2-Piperazinylquinazoline; 1-Quinazolin-2-ylpiperazine; 3-Azaquipazine
Drug classSerotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Identifiers
  • 2-piperazin-1-ylquinazoline
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC12H14N4
Molar mass214.272 g·mol−1
3D model (JSmol)
  • C1CN(CCN1)C2=NC3=CC=CC=C3C=N2
  • InChI=1S/C12H14N4/c1-2-4-11-10(3-1)9-14-12(15-11)16-7-5-13-6-8-16/h1-4,9,13H,5-8H2
  • Key:NRQJIAVOKMKUOR-UHFFFAOYSA-N

VCU-1012, also known as 1-quinazolin-2-ylpiperazine or as 3-azaquipazine, is a psychedelic drug of the arylpiperazine family related to quipazine (1-(2-quinolinyl)piperazine).[1][2][3] It is a serotonin 5-HT2A receptor agonist and produces psychedelic-like effects in rodents similarly to quipazine, but lacks quipazine's serotonin 5-HT3 receptor agonism and associated gastrointestinal adverse effects like nausea and vomiting.[1][2][3] The drug represents a novel structural class of psychedelics distinct from existing scaffolds.[1][2][3][4]

Interactions

See also: Psychedelic drug § Interactions, and Trip killer § Serotonergic psychedelic antidotes

Pharmacology

Pharmacodynamics

VCU-1012 is an agonist of the serotonin 5-HT2A receptor.[1][2] It shows about half the affinity of quipazine for the serotonin 5-HT2A receptor (Ki = 986 nM and 1,777 nM, respectively).[1] The drug is a partial agonist of the serotonin 5-HT2A receptor, with about half the activational potency of quipazine (VCU-1012, EC50Tooltip half-maximal effective concentration = 1,550 nM; EmaxTooltip maximal efficacy = 46%; quipazine, EC50Tooltip half-maximal effective concentration = 240 nM; EmaxTooltip maximal efficacy = 56%).[1]

In addition to the serotonin 5-HT2A receptor, VCU-1012 shows high affinity for the serotonin 5-HT2B receptor (Ki = 24–31 nM) and for the 5-HT3 receptor (Ki = 8.3–14 nM).[1] It also shows affinity for a variety of other receptors and for monoamine transporters, including the norepinephrine transporter (NET) and the serotonin transporter (SERT).[1] Although VCU-1012 binds to the serotonin 5-HT3 receptor, unlike quipazine, it does not act as an agonist of this receptor.[1][2] Relatedly, VCU-1012 did not produce the gastrointestinal effects of quipazine in rodents and would be expected to lack associated side effects like nausea and vomiting in humans.[1][2] It is unknown whether VCU-1012 acts pharmacologically as a serotonin 5-HT3 receptor antagonist.[1] It is also unclear whether it acts as an agonist or antagonist at the serotonin 5-HT2B receptor.[1]

The drug dose-dependently and robustly induces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.[1][2] This is fully blocked by the serotonin 5-HT2A receptor antagonist volinanserin.[1] VCU-1012 produces prolonged antidepressant-like effects in rodents.[1][2] It also produces anxiolytic-like effects.[1] The drug produces psychoplastogenic effects as well, which were mediated by serotonin 5-HT2A receptor activation.[1][2]

Chemistry

VCU-1012, along with quipazine, represents a novel structural class of psychedelics distinct from tryptamines, phenethylamines, and lysergamides.[1][2][3]

Synthesis

The chemical synthesis of VCU-1012 has been described.[1]

Analogues

Other novel psychedelic analogues of quipazine besides VCU-1012 have also been described.[1][5][6][7][8][9][4] Notable psychedelic analogues of VCU-1012 besides quipazine include 2-naphthylpiperazine (2-NP) and VCU-1021 (3-methoxyquipazine).[1]

History

VCU-1012 was first described in the scientific literature by Jessica Maltman and Richard Glennon and colleagues at Virginia Commonwealth University (VCU) in 2024.[2][3][1] It may have therapeutic potential and possible medical applications.[2][1]

See also

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w Younkin J, Bansode AH, Saha S, Paymode A, Maltman JL, Jones CB, et al. (July 2026). "Design of a new psychedelic quipazine analog with therapeutic efficacy and potentially fewer side effects". Sci Signal. 19 (947) eadw6055. doi:10.1126/scisignal.adw6055. PMID 42479815.
  2. ^ a b c d e f g h i j k l Maltman JL, Younkin J, Ghorpade A, Fiorillo M, Jaster A, Akbarali HI, et al. (5 October 2024). Characterization of the psychedelic quipazine analog VCU-1012 in mice (PDF). Neuroscience 2024. Society for Neuroscience.
  3. ^ a b c d e Maltman JL, Younkin J, Fiorillo M, Jaster AM, Paymode A, Saha S, et al. Characterizing the Novel Quipazine Analog VCU-1012: Unveiling a New Class of Psychedelic Compounds. The 48th Annual Meeting of the Japanese Neuroscience Society, July 24-27, 2025, Venue Toki Messee, Niigata, Japan. Japanese Neuroscience Society.
  4. ^ a b Glennon RA, Dukat M (2 May 2023). "Quipazine: Classical hallucinogen? Novel psychedelic?". Australian Journal of Chemistry. 76 (5): 288–298. doi:10.1071/CH22256. ISSN 0004-9425.
  5. ^ "Notes from the International Society for Research on Psychedelics' 2024 Conference in New Orleans (Guest Contribution)". Psychedelic Alpha. 20 March 2024. Retrieved 10 May 2025. Dr. Jason Younkin, a postdoctoral researcher at Virginia Commonwealth University and adjunct professor at Virginia State University, gave a talk and displayed interesting findings with quipazine analogs during the poster session. Quipazine is a unique psychedelic as its chemical structure includes a piperazine group. While it produces psychedelic effects, it is not used as frequently as other serotonergic psychedelics due to its effects on the gastrointestinal tract via 5-HT3 receptor activation. The goal of this study was to find analogs of quipazine that do not produce these negative side effects or the hallucination-like effects of all classical psychedelics using a battery of molecular and pharmacological techniques. [Photograph]
  6. ^ Younkin J (16 February 2024). Pharmacological characterization of quipazine analogs as a new structural class of psychedelic 5-HT2A receptor agonists (PDF). International Society for Research on Psychedelics (ISRP) Conference, New Orleans, Louisiana, USA, February 16-18, 2024. International Society for Research on Psychedelics. Archived from the original (PDF) on 28 February 2024.
  7. ^ Yang Y (2025). Design and Synthesis of Quipazine Analogs for Programmable Control of Psychedelic Effects (Thesis). Columbia University. doi:10.7916/0K6K-YC03. To better understand how to potentially regulate these effects, we focused on the design of compounds with programmable psychedelic intensity through fine-tuning the 5-HT2A receptor signaling efficacy. We turned to the source that drives the psychedelic effects of serotonergic psychedelics, the 5-HT2A receptor. By modifying the scaffold of quipazine, we aimed to control the psychedelic intensity by tuning different levels of 5-HT2A signaling efficacy within the quipazine analog series, and thus provide design guidelines for developing desirable pharmacological agents with varying degree of psychedelic effects.
  8. ^ de la Fuente Revenga M, Shah UH, Nassehi N, Jaster AM, Hemanth P, Sierra S, et al. (March 2021). "Psychedelic-like Properties of Quipazine and Its Structural Analogues in Mice". ACS Chemical Neuroscience. 12 (5): 831–844. doi:10.1021/acschemneuro.0c00291. PMC 7933111. PMID 33400504.
  9. ^ de la Fuente Revenga M, Shah U, González-Maeso J (19 October 2019). Non-psychedelic serotonin 5-HT2A receptor agonists: Behavioral and functional diversity in quipazine analogues (PDF). International Society for Research on Psychedelics (ISRP), Inaugural Conference, New Orleans, Louisiana, USA, October 18-20, 2019. International Society for Research on Psychedelics (ISRP). Archived from the original (PDF) on 21 November 2021.

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