DPAI

Pharmaceutical compound From Wikipedia, the free encyclopedia

DPAI, also known as 4-(N,N-dipropylaminoethyl)indole (4-DPAEI), 2-desoxo-2-ene-ropinirole, or BD-179, is a dopamine receptor agonist and partial ergoline closely related to the clinically used dopamine receptor agonist and antiparkinsonian agent ropinirole.^[1]^[2]^[3]^[4]

Other names4-(N,N-Dipropylaminoethyl)indole; 4-DPAEI; 2-Desoxo-2-ene-ropinirole; BD-179; BD179

Drug classDopamine receptor agonist; Prolactin inhibitor

ATC code

None

CAS Number

76149-15-0

Quick facts Clinical data, Other names ...

DPAI
Clinical data

Other names	4-(N,N-Dipropylaminoethyl)indole; 4-DPAEI; 2-Desoxo-2-ene-ropinirole; BD-179; BD179
Drug class	Dopamine receptor agonist; Prolactin inhibitor
ATC code	None
Identifiers
IUPAC name N-[2-(1H-indol-4-yl)ethyl]-N-propylpropan-1-amine
CAS Number	76149-15-0
PubChem CID	3086054
ChemSpider	2342766
ChEMBL	ChEMBL67040
CompTox Dashboard (EPA)	DTXSID10227004
Chemical and physical data
Formula	C₁₆H₂₄N₂
Molar mass	244.382 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CCCN(CCC)CCC1=C2C=CNC2=CC=C1
InChI InChI=1S/C16H24N2/c1-3-11-18(12-4-2)13-9-14-6-5-7-16-15(14)8-10-17-16/h5-8,10,17H,3-4,9,11-13H2,1-2H3 Key:AFRBPRLOPBAGCM-UHFFFAOYSA-N

It has a delayed onset of effects and weak actions in vitro, suggestive that it may be a metabolically activated prodrug via 6-hydroxylation into its metabolite 6-HO-DPAI (TL-350).^[5]^[2]^[3]^[6]^[4] The drug is said to be a highly selective agonist of presynaptic dopamine autoreceptors, with little or no activity at postsynaptic dopamine receptors.^[1]^[7]^[8]^[9] It dramatically reduces dopamine release in the caudate nucleus, produces hypolocomotion, and strongly suppresses prolactin secretion in rodents.^[1]^[8]^[9]^[10]^[11] No effects of DPAI on serotonin receptors have been reported, at least as of 1982.^[12]

DPAI was first described in the scientific literature by 1980.^[3]^[1] It was developed independently by David E. Nichols and colleagues and by another group of researchers.^[11] Analogues of DPAI in which its propyl groups have been replaced with other alkyl groups such as methyl or ethyl groups have also been studied.^[4]^[11]

Chemical structures of DPAI and analogues

References

[1]
Clemens JA, Kornfeld EC, Phebus LA, Shaar CJ, Smalstig EB, Cassady JM, et al. (1982). Dopaminergic Agents Related to Ergolines. In The Chemical Regulation of Biological Mechanisms. The Proceedings of the 1st Medicinal Chemistry Symposium, Cambridge, England, 27th-30 September 1981. Vol. 42. London: Royal Society of Chemistry. p. 167.
[2]
Nichols DE (29 June 1983). "The Development of Novel Dopamine Agonists". Dopamine Receptors. ACS Symposium Series. Vol. 224. Washington, D.C.: American Chemical Society. pp. 201–222. doi:10.1021/bk-1983-0224.ch009. ISBN 978-0-8412-0781-3. The situation seems further confounded by the reports (13) of dopaminergic activity for the 4-substituted aminoethylindole DPAI, IX. However, the delayed onset of action reported by Cannon et al . (13) for this compound, as well as a weak in vitro action (14), lead to the possibility that DPAI may be metabolically activated by hydroxylation at the 6-position. This is a common transformation for indoles. Indeed, lergotrile is hydroxylated at the corresponding 13 position to yield a metabolite which is an order of magnitude more potent than lergotrile itself (15).
[3]
Bach NJ, Kornfeld EC, Jones ND, Chaney MO, Dorman DE, Paschal JW, et al. (May 1980). "Bicyclic and tricyclic ergoline partial structures. Rigid 3-(2-aminoethyl)pyrroles and 3- and 4-(2-aminoethyl)pyrazoles as dopamine agonists". Journal of Medicinal Chemistry. 23 (5): 481–491. doi:10.1021/jm00179a003. PMID 7189782.
[4]
Koons JC, Long JP, Cannon JG (December 1984). "In vivo and in vitro dopaminergic effects of three ergoline fragments". Naunyn Schmiedebergs Arch Pharmacol. 328 (2): 180–185. doi:10.1007/BF00512069. PMID 6527705.
[5]
Wikström H, Lii JH, Allinger NL (October 1987). "The dopaminergic moiety of the ergots: a controversial topic studied with molecular mechanics". Journal of Medicinal Chemistry. 30 (10): 1928–1934. doi:10.1021/jm00393a041. PMID 3656365. In the first publication on DPAI it was implied that this compound might have to be bioactivated before excerting its effect.10 Consequently, the same authors later showed that 6-OH-DPAI (10) really is more active than DPAI itself, and in addition, it is active in vitro and has no lag period before excerting its effect in vivo, which is the case with DPAI.21 This very interesting finding is fully in concert with the previously discussed metabolic activation, i.e., the 13-hydroxylation of the ergots.
[6]
Cannon JG, Lee T, Ilhan M, Koons J, Long JP (March 1984). "6-Hydroxy-4-[2-(di-n-propylamino)ethyl]indole: synthesis and dopaminergic actions". Journal of Medicinal Chemistry. 27 (3): 386–389. doi:10.1021/jm00369a026. PMID 6699883.
[7]
Clark D, Hjorth S, Carlsson A (1985). "Dopamine-receptor agonists: mechanisms underlying autoreceptor selectivity. I. Review of the evidence". Journal of Neural Transmission. 62 (1–2): 1–52. doi:10.1007/BF01260414. PMID 3894582. Also of considerable interest are those agonists which have been suggested to act selectively at DA autoreceptors. These include racemic 3-PPP (Hjorth et al., 1980, 1981), DPAI (Clemens et al., 1984), EMD 23448 (Chiodo and Bunney, 1983) and B-HT 920 (Anden et al, 1983 a, b, c), [...]
[8]
Clark D, Hjorth S, Carlsson A (1985). "Dopamine receptor agonists: mechanisms underlying autoreceptor selectivity. II. Theoretical considerations". Journal of Neural Transmission. 62 (3–4): 171–207. doi:10.1007/BF01252236. PMID 2863323. This suggestion was in part based on work with various DA antagonists considered to possess differential blocking capacity at DA autoreceptors vs. postsynaptic receptors. In further support of this interpretation, TDHL (Wachtd and Dorow, 1983), DPAI (Clemens et al., 1984) and B-HT 920 (And~n et al., 1983 a, b) all lack intrinsic activity at normosensitive postsynaptic DA receptors but strongly reduce serum prolactin levels (Clemens et aL, 1984; Wachtel and Dorow, 1983; Eriksson et al., 1985).
[9]
Clemens JA, Fuller RW, Phebus LA, Smalstig EB, Hynes MD, Cassady JM, et al. (March 1984). "Stimulation of presynaptic dopamine autoreceptors by 4-(2-di-n-propylaminoethyl) indole (DPAI)". Life Sciences. 34 (11): 1015–1022. doi:10.1016/0024-3205(84)90014-6. PMID 6422174.
[10]
Nichols DE, Cassady JM, Persons PE, Yeung MC, Clemens JA, Smalstig EB (September 1989). "Synthesis and evaluation of N,N-di-n-propyltetrahydrobenz[f]indol-7-amine and related congeners as dopaminergic agonists". Journal of Medicinal Chemistry. 32 (9): 2128–2134. doi:10.1021/jm00129a017. PMID 2570151.
[11]
Persons P, Mayer J, Nichols D, Cassady J, Smalstig E, Clemens J (1991). "Preliminary evaluation of 4-(2-N,N-dialkylaminoethyl)indoles as potential dopamine agonists". European Journal of Medicinal Chemistry. 26 (4). Elsevier BV: 473–475. doi:10.1016/0223-5234(91)90110-9. ISSN 0223-5234.
[12]
Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikström H, Arvidsson LE, et al. (1982). "8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity". Journal of Neural Transmission. 55 (3): 169–188. doi:10.1007/BF01276574. ISSN 0300-9564. Retrieved 10 February 2026. The original suggestion by Nichols (1976), that the pyrroleethylamine moiety of the ergots confers dopaminergic properties to drugs of this class was recently experimentally substantiated by Bach et al. (1980), showing that "debenzergoline" (Fig. 4; 6) is a potent dopaminergic stimulant which appears to lack the 5-HT agonistic (or antagonistic) effects seen with many of the ergot derivatives. However, on the basis of results obtained with 4-(2-[di-n-propylamino]ethyl)indole (DPAI) (Fig. 4; 4) containing the A and B rings of the ergots, Cannon et al. (1981) have challenged the view as to which is the dopaminergic pharmacophore of drugs belonging to the ergot class. No effects of DPAI on 5-HT systems have so far been reported.

DPAI

See also

References

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