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AHR-1709

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AHR-1709
Clinical data
Other namesMPTP N-ethylindole
Drug classSerotonin receptor modulator; Serotonin 5-HT1A receptor antagonist; Serotonin 5-HT2A receptor antagonist; Dopamine receptor modulator
ATC code
  • None
Identifiers
  • 3-[2-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)ethyl]-1H-indole
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC21H22N2
Molar mass302.421 g·mol−1
3D model (JSmol)
  • C1CN(CC=C1C2=CC=CC=C2)CCC3=CNC4=CC=CC=C43
  • InChI=1S/C21H22N2/c1-2-6-17(7-3-1)18-10-13-23(14-11-18)15-12-19-16-22-21-9-5-4-8-20(19)21/h1-10,16,22H,11-15H2
  • Key:ANEFQMOYWNJZFI-UHFFFAOYSA-N

AHR-1709 is an experimental antipsychotic of the tryptamine family which was never marketed.[1][2] It is a cyclized tryptamine, more specifically an analogue of pip-tryptamine.[1][2]

Pharmacology

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Pharmacodynamics

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AHR-1709 shows high affinity for the serotonin 5-HT1A and 5-HT2A receptors (Ki = 27–44 nM and 4.8 nM, respectively)[2][3] and for the dopamine D2 receptor (Ki = 81 nM).[4] It may act as a serotonin 5-HT1A receptor antagonist.[3] The drug also shows high affinity for ketanserin-labeled serotonin 5-HT2A receptors (Ki = 9.33–12.6 nM) and is a potent antagonist of these receptors (A2 = 24.6–120 nM).[5][6]

The drug produces antipsychotic-like effects in rodents, including reversal of hyperlocomotion but without induction of catalepsy, antagonism of stereotypy, or elevation of prolactin levels.[1][7][8] AHR-1709 also produces antiemetic effects in rodents.[1]

It is a derivative of the dopaminergic neurotoxin MPTP and is a weak dopamine reuptake inhibitor similarly but with 23-fold higher potency (IC50Tooltip half-maximal inhibitory concentration = 4,200 nM and 95,200 nM, respectively).[9] However, unlike MPTP, AHR-1709 did not produce dopaminergic neurotoxicity in rodents.[9]

Chemistry

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A number of derivatives of AHR-1709 have been described.[7][2][3] An analogue of AHR-1709 with an elongated side chain is EMD-23448.[4] AHR-1709 is also structurally similar to pertines like oxypertine.[7]

History

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AHR-1709 was first described in the scientific literature by 1978.[1]

See also

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References

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  1. 1 2 3 4 5 Costall B, Funderburk WH, Leonard CA, Naylor RJ (December 1978). "Assessment of the neuroleptic potential of some novel benzamide, butyrophenone, phenothiazine and indole derivatives". The Journal of Pharmacy and Pharmacology. 30 (12): 771–778. doi:10.1111/j.2042-7158.1978.tb13390.x. PMID 32242.
  2. 1 2 3 4 Taylor EW (1985). The Development of Indoleamine Derivatives Selective for Subtypes of Serotonin Receptors (TRYPTAMINE, BASILAR ARTERY, ANTAGONIST, ERGOLINE, SYNTHESIS) (Ph.D. thesis). The University of Arizona.
  3. 1 2 3 Cornfield LJ (1990). Characterization of structure-activity relationships for serotonin receptors coupled to adenylate cyclase (Ph.D. thesis). The University of Arizona.
  4. 1 2 Böttcher H, Barnickel G, Hausberg HH, Haase AF, Seyfried CA, Eiermann V (October 1992). "Synthesis and dopaminergic activity of some 3-(1,2,3,6-tetrahydro-1-pyridylalkyl)indoles. A novel conformational model to explain structure-activity relationships". Journal of Medicinal Chemistry. 35 (22): 4020–4026. doi:10.1021/jm00100a006. PMID 1359142.
  5. ↑ Killam AL, Nikam SS, Lambert GM, Martin AR, Nelson DL (March 1990). "Comparison of two different arterial tissues suggests possible 5-hydroxytryptamine2 receptor heterogeneity". The Journal of Pharmacology and Experimental Therapeutics. 252 (3): 1083–1089. doi:10.1016/S0022-3565(25)20164-1. PMID 2319460.
  6. ↑ Killam AL (1990). Characterization of vascular serotonin receptors (Ph.D. thesis). The University of Arizona.
  7. 1 2 3 Costall B, Dannenburg WN, Johnson DN, Naylor RJ (April 1983). "Aminoalkylindoles: atypical dopamine antagonists". The Journal of Pharmacy and Pharmacology. 35 (4): 229–233. doi:10.1111/j.2042-7158.1983.tb02918.x. PMID 6133932.
  8. ↑ Paulis TD (1983). "Chapter 3. Antipsychotic Agents and Dopamine Agonists". Annual Reports in Medicinal Chemistry. Vol. 18. Elsevier. pp. 21–30. doi:10.1016/S0065-7743(08)60758-7. ISBN 978-0-12-040518-3.
  9. 1 2 Baldessarini RJ, Kula NS, Francoeur D, Finklestein SP, Murphy F, Neumeyer JL (November 1986). "Synthetic analgesics and other phenylpiperidines: effects on uptake and storage of dopamine and other monoamines mouse forebrain tissue". Life Sciences. 39 (19): 1765–1777. doi:10.1016/0024-3205(86)90096-2. PMID 3490612.
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