UH-232

Overview

UH-232, or (+)-UH-232, also known as 5-hydroxy-1-methyl-2-(dipropylamino)tetralin methyl ether (5-HMDPTME), is a dopamine and serotonin receptor modulator of the 2-aminotetralin family which was under development for the treatment of schizophrenia but was never marketed. It is taken orally. Contrary to expectations, the drug did not end up producing antipsychotic effects in clinical trials. Instead, it was reported to produce stimulant, hallucinogenic, and psychosis-exacerbating effects.[1–4] WP

Drug class

Dopamine D2 receptor antagonist Dopamine D3 receptor weak partial agonist Serotonin 5-HT2A receptor agonist Hallucinogen Serotonergic psychedelic WP

From the Wikipedia article's infobox.

Uses, dosage and effects

Use and effects

UH-232 has been reported to produce stimulant, hallucinogenic, and psychosis-exacerbating effects in humans. The hallucinogenic effects of UH-232 have been reported to include "perceptual disturbances", "illusions", "aberrations of perception of auditory, visual and tactile stimuli", and "visual hallucinations". Based on preclinical findings, it has been theorized that the hallucinogenic effects of UH-232 may be due to serotonin 5-HT2A receptor agonism and hence that it may be a serotonergic psychedelic.[2–6] WP

Pharmacology

Pharmacodynamics

UH-232 is a dopamine D₂ and D₃ receptor antagonist or weak partial agonist. It shows about 3- or 4-fold selectivity or higher affinity for the dopamine D₃ receptor over the dopamine D₂ receptor (Kᵢ = 4.2–11 nM and 15–40 nM, respectively). The drug is an antagonist at dopamine D₂Sh autoreceptors on dopaminergic nerve terminals. It also interacts with the dopamine D₄ receptor to a much lesser extent (Kᵢ = 48–100 nM). The drug's activational efficacy is 16% at the dopamine D₂ receptor, 16 to 40% at the dopamine D₃ receptor, and 15% at the dopamine D₄ receptor. However, it showed more than 1,000-fold lower activational potency at the dopamine D₄ receptor than at the dopamine D₂ and D₃ receptors. It is said to be unknown whether UH-232 is a functional antagonist or partial agonist of the dopamine receptors in humans.[3][7–15] WP

In addition to the dopamine D₂ and D₃ receptors, UH-232 shows affinity for the dopamine D₁ receptor (Kᵢ = 159 nM), serotonin 5-HT₂ receptor (Kᵢ = 118 nM), and 5-HT1A receptor (Kᵢ = 144–168 nM). Its affinity for the serotonin 5-HT₂ receptor is around 10-fold lower than for the dopamine D₂ and D₃ receptors. The drug has been reported to increase serotonin 5-HT₂ receptor-mediated phosphoinositol turnover in fibroblasts transfected with the rat serotonin 5-HT2A receptor, suggesting that it may act as a serotonin 5-HT2A receptor agonist. Accordingly, UH-232 produced hallucinogenic effects in humans.[2][3][4][8] WP

UH-232 produces hyperlocomotion (a stimulant-like effect) at low doses and mild hypolocomotion at high doses. It also produces weak stereotypies. The stimulant-like effects of UH-232 have been thought to be due to preferential dopamine autoreceptor antagonism and consequent disinhibition of dopamine release. However, they might also be related to postsynaptic D₃ receptor antagonism. Another possibility is that serotonin 5-HT2A receptor activation may be involved in its stimulant-like effects. UH-232 produces synergistic and marked hyperlocomotion in combination with a subthreshold dose of the NMDA receptor antagonist dizocilpine (MK-801) in monoamine-depleted rodents, an effect that can be antagonized by dopamine D₁ and D₂ receptor antagonists and by the serotonin 5-HT₂ receptor antagonist ritanserin.[3][4][12][16][17][18] WP

UH-232 stimulates prolactin secretion in rodents. It has been found to antagonize the hyperlocomotion or stimulant-like effects of cocaine, dextroamphetamine, and apomorphine in rodents. The drug also antagonized their reinforcing effects in rodents. However, it did not antagonize the interoceptive effects of cocaine in rodent drug discrimination tests. In addition, it was able to partly substitute for cocaine in these tests.[19–22] WP

Pharmacokinetics

The oral bioavailability of UH-232 is 3.7% and elimination half-life is 2.5 hours in rats.[8] WP

Research

Research

UH-232 was under development for the treatment of schizophrenia. It reached phase 1 clinical trials for this indication before development was discontinued. The drug did not improve symptoms of schizophrenia in a small trial. Instead, it appeared to exacerbate symptoms, including increasing unusual thought content, anxiety, activation, and hostility. Besides treatment of schizophrenia, UH-232 has been proposed for potential use in the diagnosis of early-stage Parkinson's disease.[1][2][3][23] WP

History

History

UH-232 was first described in the scientific literature by Arvid Carlsson and colleagues by 1986. It was developed by AstraZeneca. A clinical study of UH-232 for treatment of schizophrenia was published in 1998. It was also evaluated in healthy volunteers, in whom it unexpectedly produced hallucinogenic effects.[1–4][12][16][19] WP

Chemistry

Formula

C18H29NO PC

CAS number

95999-12-5 PC

Molar mass (g/mol)

275.4 PC

IUPAC name (computed by PubChem)

(1S,2R)-5-methoxy-1-methyl-N,N-dipropyl-1,2,3,4-tetrahydronaphthalen-2-amine PC

SMILES

CCCN(CCC)[C@@H]1CCC2=C([C@@H]1C)C=CC=C2OC PC

InChIKey

BTOJYCTUJJHANF-WMLDXEAASA-N PC

PubChem CID

6604756

IUPAC name

(1S,2R)-5-methoxy-1-methyl-N,N-dipropyl-1,2,3,4-tetrahydronaphthalen-2-amine WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Delving into the Latest Updates on UH-232 with Synapse. 16 May 2026
2. Journal / agency Carlsson ML, Carlsson A, Nilsson M. Schizophrenia: from dopamine to glutamate and back. Current Medicinal Chemistry. February 2004. doi:10.2174/0929867043456034 · PMID 14965231
3. Journal / agency Lahti AC, Weiler M, Carlsson A, Tamminga CA. Effects of the D3 and autoreceptor-preferring dopamine antagonist (+)-UH232 in schizophrenia. Journal of Neural Transmission. 1998. doi:10.1007/s007020050091 · PMID 9826114
4. Journal / agency Carlsson ML. The selective 5-HT2A receptor antagonist MDL 100,907 counteracts the psychomotor stimulation ensuing manipulations with monoaminergic, glutamatergic or muscarinic neurotransmission in the mouse--implications for psychosis. Journal of Neural Transmission. General Section. 1995. doi:10.1007/BF01276460 · PMID 8748668
5. Journal / agency Strange PG. Antipsychotic drug action: antagonism, inverse agonism or partial agonism. Trends in Pharmacological Sciences. June 2008. doi:10.1016/j.tips.2008.03.009 · PMID 18471899
6. Journal / agency Roth BL, Sheffler DJ, Kroeze WK. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nature Reviews. Drug Discovery. April 2004. doi:10.1038/nrd1346 · PMID 15060530
7. Journal / agency Coldwell MC, Boyfield I, Brown AM, Stemp G, Middlemiss DN. Pharmacological characterization of extracellular acidification rate responses in human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells. British Journal of Pharmacology. July 1999. doi:10.1038/sj.bjp.0702657 · PMID 10455259 · PMC1566129
8. Journal / agency Haadsma-Svensson SR, Smith MW, Lin CH, Neil Duncan J, Sonesson C, Wikström HK, Waters N, Carlsson A, Svensson K. Synthesis and biological activity of C-5 modified derivatives of (+)-AJ76 and (+)-UH232: Increased dopamine D3 receptor preference and improved pharmacokinetic properties. Bioorganic & Medicinal Chemistry Letters. 1994. doi:10.1016/S0960-894X(01)80181-5
9. Journal / agency Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. September 1990. doi:10.1038/347146a0 · PMID 1975644
10. Journal / agency Sokoloff P, Giros B, Martres MP, Andrieux M, Besancon R, Pilon C, Bouthenet ML, Souil E, Schwartz JC. Localization and function of the D3 dopamine receptor. Arzneimittel-Forschung. February 1992. PMID 1586393
11. Other PDSPKiDatabase
12. Journal / agency Svensson K, Johansson AM, Magnusson T, Carlsson A. (+)-AJ 76 and (+)-UH 232: central stimulants acting as preferential dopamine autoreceptor antagonists. Naunyn-Schmiedeberg's Archives of Pharmacology. November 1986. doi:10.1007/BF00508777 · PMID 2880302
13. Journal / agency Waters N, Lagerkvist S, Löfberg L, Piercey M, Carlsson A. The dopamine D3 receptor and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232; a microdialysis study. European Journal of Pharmacology. September 1993. doi:10.1016/0014-2999(93)90075-S · PMID 8253112
14. Journal / agency Aretha CW, Sinha A, Galloway MP. Dopamine D3-preferring ligands act at synthesis modulating autoreceptors. The Journal of Pharmacology and Experimental Therapeutics. August 1995. PMID 7636720
15. Journal / agency Griffon N, Pilon C, Schwartz JC, Sokoloff P. The preferential dopamine D3 receptor ligand, (+)-UH232, is a partial agonist. European Journal of Pharmacology. August 1995. doi:10.1016/0014-2999(95)00460-3 · PMID 7498261
16. Journal / agency Svensson K, Hjorth S, Clark D, Carlsson A, Wikström H, Andersson B, Sanchez D, Johansson AM, Arvidsson LE, Hacksell U. (+)-UH 232 and (+)-UH 242: novel stereoselective dopamine receptor antagonists with preferential action on autoreceptors. Journal of Neural Transmission. 1986. doi:10.1007/BF01249608 · PMID 3083041
17. Journal / agency Sotnikova TD, Gainetdinov RR, Grekhova TV, Rayevsky KS. Effects of intrastriatal infusion of D2 and D3 dopamine receptor preferring antagonists on dopamine release in rat dorsal striatum (in vivo microdialysis study). Pharmacological Research. March 2001. doi:10.1006/phrs.2000.0773 · PMID 11401421
18. Journal / agency Svensson A, Carlsson M, Carlsson A. Synergistic interactions between the NMDA antagonist dizocilpine and the preferential dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 with regard to locomotor stimulation in monoamine-depleted mice. Journal of Neural Transmission. General Section. 1991. doi:10.1007/BF01244659 · PMID 1867840
19. Journal / agency Svensson K, Carlsson M, Carlsson A, Hjorth S, Johansson AM, Eriksson E. The putatively selective dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 stimulate prolactin release in rats. European Journal of Pharmacology. November 1986. doi:10.1016/0014-2999(86)90273-6 · PMID 3792447
20. Journal / agency Piercey MF, Lum JT, Hoffmann WE, Carlsson A, Ljung E, Svensson K. Antagonism of cocaine's pharmacological effects by the stimulant dopaminergic antagonists, (+)-AJ76 and (+)-UH232. Brain Research. August 1992. doi:10.1016/0006-8993(92)91578-3 · PMID 1393576
21. Journal / agency Kling-Petersen T, Ljung E, Svensson K. The preferential dopamine autoreceptor antagonist (+)-UH232 antagonizes the positive reinforcing effects of cocaine and d-amphetamine in the ICSS paradigm. Pharmacology, Biochemistry, and Behavior. October 1994. doi:10.1016/0091-3057(94)90432-4 · PMID 7824548
22. Journal / agency Callahan PM, Piercey MF, Cunningham KA. Effects of the putative dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 on the discriminative stimulus properties of cocaine. Psychopharmacology. 1992. doi:10.1007/BF02244968 · PMID 1589564
23. Journal / agency Zhou J, Li J, Papaneri AB, Cui G. AJ76 and UH232 as potential agents for diagnosing early-stage Parkinson's disease. Neuropharmacology. March 2023. doi:10.1016/j.neuropharm.2022.109397 · PMID 36623805 · PMC9901527

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