Dihydrexidine

Last updated
Dihydrexidine
Dihydrexidine structure.png
Clinical data
Other namesIP-202; IP202; DAR-0100; DAR0100; DAR-100; DAR100
Drug class Dopamine receptor agonist; Dopamine D1-like receptor agonist
ATC code
  • None
Identifiers
  • 5,6,6a,7,8,12b-hexahydro-benzo(a)phenanthridine-10,11-diol
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C17H17NO2
Molar mass 267.328 g·mol−1
3D model (JSmol)
  • c1ccc2c(c1)CN[C@H]3[C@H]2c4cc(c(cc4CC3)O)O
  • InChI=1S/C17H17NO2/c19-15-7-10-5-6-14-17(13(10)8-16(15)20)12-4-2-1-3-11(12)9-18-14/h1-4,7-8,14,17-20H,5-6,9H2/t14-,17-/m1/s1 X mark.svgN
  • Key:BGOQGUHWXBGXJW-RHSMWYFYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Dihydrexidine (developmental code names IP-202 and DAR-0100) is a moderately selective full agonist at the dopamine D1 and D5 receptors. [1] [2] [3] It has approximately 10-fold selectivity for D1 and D5 over the D2 receptor. [4] Although dihydrexidine has some affinity for the D2 receptor, it has functionally selective (highly biased) actions on dopamine D2 receptor signaling, [5] thereby explaining why it lacks dopamine D2 receptor agonist behavioral qualities. [6]

Dihydrexidine has shown impressive antiparkinson effects in the MPTP-primate model, [7] and has been investigated for the treatment of Parkinson's disease. [8] In an early clinical trial the drug was given intravenously and led to profound hypotension so development was halted. [9] The drug was resurrected when it was shown that smaller subcutaneous doses were safe. [10] This led to a pilot study in schizophrenia [11] and current clinical trials to assess its efficacy in improving the cognitive and working memory deficits in schizophrenia and schizotypal disorder.

There have been several reviews of relevance to the compound. [12] [13] [14]

See also

References

  1. ↑ "Dihydrexidine". AdisInsight. 18 June 1997. Retrieved 31 January 2026.
  2. ↑ "DAR 100". AdisInsight. 28 July 2015. Retrieved 31 January 2026.
  3. ↑ Lovenberg TW, Brewster WK, Mottola DM, Lee RC, Riggs RM, Nichols DE, Lewis MH, Mailman RB (1989). "Dihydrexidine, a novel selective high potency full dopamine D-1 receptor agonist". Eur J Pharmacol. 166 (1): 111–113. doi:10.1016/0014-2999(89)90690-0. PMID   2572425.
  4. ↑ Mottola DM, Brewster WK, Cook LL, Nichols DE, Mailman RB (1992). "Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist". J Pharmacol Exp Ther. 262 (1): 383–393. PMID   1352553.
  5. ↑ Kilts, JD.; et al. (2002). "Functional selectivity of dopamine receptor agonists. II. Actions of dihydrexidine in D2L receptor-transfected MN9D cells and pituitary lactotrophs". J Pharmacol Exp Ther. 301 (3): 1179–89. doi:10.1124/jpet.301.3.1179. PMID   12023553.
  6. ↑ Darney KJ Jr, Lewis MH, Brewster WK, Nichols DE, Mailman RB (1991). "Behavioral effects in the rat of dihydrexidine, a high-potency, full-efficacy D1 dopamine receptor agonist". Neuropsychopharmacology. 5 (3): 187–195. PMID   1684499.
  7. ↑ Taylor JR, Lawrence MS, Redmond DE Jr, Elsworth JD, Roth RH, Nichols DE, Mailman RB (1991). "Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys". Eur J Pharmacol. 199 (3): 389–391. doi: 10.1016/0014-2999(91)90508-N . PMID   1680717.
  8. ↑ Mailman RB, Nichols DE (1998). "Dopamine D1 receptor agonists as antiparkinson drugs". Trends Pharmacol. Sci. 19 (7): 255–256. doi:10.1016/S0165-6147(98)01219-X. PMID   9703756.
  9. ↑ Blanchet PJ, Fang J, Gillespie M, Sabounjian L, Locke KW, Gammans R, Mouradian MM, Chase TN (1998). "Effects of the full dopamine D1 receptor agonist dihydrexidine in Parkinson's disease". Clin. Neuropharmacol. 21 (6): 339–343. PMID   9844789.
  10. ↑ George MS, Molnar CE, Grenesko EL, Anderson B, Mu Q, Johnson K, Nahas Z, Knable M, Fernandes P, Juncos J, Huang X, Nichols DE, Mailman RB (2007). "A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia". Schizophr. Res. 93 (1–3): 42–50. doi:10.1016/j.schres.2007.03.011. PMID   17467956. S2CID   31375175.
  11. ↑ Mu Q, Johnson K, Morgan PS, Grenesko EL, Molnar CE, Anderson B, Nahas Z, Kozel FA, Kose S, Knable M, Fernandes P, Nichols DE, Mailman RB, George MS (2007). "A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia". Schizophr. Res. 94 (1–3): 332–341. doi:10.1016/j.schres.2007.03.033. PMID   17596915. S2CID   25497605.
  12. ↑ Mailman R, Huang X, Nichols DE (2001). "Parkinson's disease and D1 dopamine receptors". Current Opinion in Investigational Drugs. 2 (11): 1582–1591. PMID   11763161.
  13. ↑ Salmi P, Isacson R, Kull B (2004). "Dihydrexidine--the first full dopamine D1 receptor agonist". CNS Drug Rev. 10 (3): 230–242. doi:10.1111/j.1527-3458.2004.tb00024.x. PMC   6741759 . PMID   15492773.
  14. ↑ Zhang J, Xiong B, Zhen X, Zhang A (2009). "Dopamine D1 receptor ligands: where are we now and where are we going". Med Res Rev. 29 (2): 272–294. doi:10.1002/med.20130. PMID   18642350. S2CID   25334596.
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