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). 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. The drug represents a novel structural class of psychedelics distinct from existing scaffolds.

Interactions

Pharmacology

Pharmacodynamics

VCU-1012 is an agonist of the serotonin 5-HT2A receptor. It shows about half the affinity of quipazine for the serotonin 5-HT2A receptor (Ki = 986 nM and 1,777 nM, respectively). 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%).

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). It also shows affinity for a variety of other receptors and for monoamine transporters, including the norepinephrine transporter (NET) and the serotonin transporter (SERT). Although VCU-1012 binds to the serotonin 5-HT3 receptor, unlike quipazine, it does not act as an agonist of this receptor. 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. It is unknown whether VCU-1012 acts pharmacologically as a serotonin 5-HT3 receptor antagonist. It is also unclear whether it acts as an agonist or antagonist at the serotonin 5-HT2B receptor.

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

Chemistry

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

Synthesis

The chemical synthesis of VCU-1012 has been described. VCU-1012 was synthesised by reacting 2-chloroquinazoline with excess piperazine in anhydrous toluene under reflux. The resulting free base was converted to its hydrochloride salt using hydrogen chloride in diethyl ether, followed by recrystallisation from methanol.

Analogues

Other novel psychedelic analogues of quipazine besides VCU-1012 have also been described. Notable psychedelic analogues of VCU-1012 besides quipazine include 2-naphthylpiperazine (2-NP) and VCU-1021 (3-methoxyquipazine).

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. It may have therapeutic potential and possible medical applications.

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 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. 1 2 3 4 5 6 7 8 9 10 11 12 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. 1 2 3 4 5 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. 1 2 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.