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Chemical Compound Review

CHEMBL285755     7-(dipropylamino)-5,6,7,8...

Synonyms: SureCN623950, AG-J-78903, DP-7-AT, CHEBI:152338, CCG-204705, ...
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Disease relevance of DP-7-AT

  • Another selective D(3) antagonist, GR218,231, mimicked S33084 in inhibiting 7-OH-DPAT-induced PEs and hypothermia but neither hypophagia nor yawning behavior [1].
  • However, pretreatment with spiperone, a D(2) receptor antagonist, did not affect the 7-OH-DPAT-induced ocular hypotension [2].
  • The R(+)enantiomer of 7-OH-DPAT (0.03-1 mg/kg, s.c.) caused emesis in a dose-dependent manner, whereas the S(-)enantiomer, even at 1 mg/kg s.c. failed to induce emesis [3].
  • However, the hyperthermia induced by SK&F 38393 was interestingly enhanced by 7-OH-DPAT and quinpirole.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
  • The effects of the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) and the DA D2/3 receptor agonist 7-OH-DPAT on core temperature was monitored in adult male Wistar rats, approximately 300 g body weight [5].

Psychiatry related information on DP-7-AT


High impact information on DP-7-AT

  • The D-3-selective compounds 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT) and quinpirole potently decreased cocaine self-administration in the rat at doses that were not by themselves reinforcing [11].
  • D2 family dopamine agonists, including low doses of the D3-preferring agonist 7-OH-DPAT, increased the numbers of Fos-like-immunoreactive neurons in the PVT [12].
  • 7-OH-DPAT-induced natriuresis also was observed in DS rats that were on normal diet but not in hypertensive DS rats that were on high-salt diet [13].
  • However, the inhibitory effects of PDBu and 7-OH-DPAT on NHE3 activity were completely abolished by A-23287 and thapsigargin [14].
  • Here, we describe studies evaluating the behavioral effects of (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) and PD 128907, two D3 receptor agonists whose in vivo selectivity has been a topic of considerable controversy [15].

Chemical compound and disease context of DP-7-AT


Biological context of DP-7-AT

  • In clearance experiments infusion of 7-OH-DPAT (0.01-1.0 microg. kg(-1). min(-1)) dose-dependently elevated glomerular filtration rate (GFR) without affecting mean arterial blood pressure (MAP) [18].
  • In renal blood flow experiments 7-OH-DPAT infusion (1.0 microg. kg(-1). min(-1)) increased GFR by 16 +/- 2%, associated with an unexpected fall in renal blood flow by 20 +/- 3% and a significant elevation of renal vascular resistance by 18 +/- 3% [18].
  • S33084 also dose dependently reduced 7-OH-DPAT-induced penile erections (PEs) but had little effect on 7-OH-DPAT-induced yawning and hypophagia, and it did not block contralateral rotation elicited by the preferential D(3) agonist quinpirole in unilateral substantia nigra-lesioned rats [1].
  • The second major finding is that the two groups of rats, which are markedly different as regards sexual typology, exhibit different behavioral responses to 7-OH-DPAT [19].
  • The magnitude of the attenuation obtained when morphine and 7-OH-DPAT were administered at the same time was similar to that obtained when administration of these drugs was separated by 6 h, indicating that 7-OH-DPAT did not alter morphine pharmacokinetics [20].

Anatomical context of DP-7-AT


Associations of DP-7-AT with other chemical compounds

  • These data indicate that 7-OH-DPAT and nafadotride increase proNT/N mRNA levels in brain areas affected by antipsychotic drugs and suggest that the D3 receptor may regulate proNT/N mRNA expression in the nucleus accumbens shell [21].
  • In the present study we investigated the renal hemodynamic effects of dopamine D(3) receptor activation by R(+)-7-hydroxy-dipropylaminotetraline (7-OH-DPAT) in thiopental-anesthetized Sprague-Dawley rats [18].
  • In contrast to TH activation due to K+ -induced depolarization, the activation evoked by tissue incubation with dibutyryl cyclic AMP was unaffected by the typical agonist 7-OH-DPAT or the antagonist (-)-sulpiride [24].
  • C1- and C3-methyl-substituted derivatives of the potent dopamine (DA) receptor agonist 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) have been synthesized, and their conformational preferences have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics (MMP2) calculations [25].
  • Chemically-diverse, preferential D3 versus D2 agonists, quinelorane, CGS15855A, pramipexole, ropinirole and piribedil, generalized to PD128,907 (and 7-OH-DPAT) in this order of potency, which correlated more strongly with affinity/activity at cloned human (h)D3 (r=0.68/0.81, n=7) than hD2 (0.27/0.64, n=7) receptors [26].

Gene context of DP-7-AT


Analytical, diagnostic and therapeutic context of DP-7-AT

  • In micropuncture experiments 7-OH-DPAT (1.0 microg. kg(-1). min(-1)) significantly elevated stop-flow pressure measured in the early proximal tubules and reduced hydrostatic pressure at the first branching point of the efferent arteriole without altering MAP [18].
  • 7-OH-DPAT (0.1-3 mg/kg) and PD 128907 (1-10 mg/kg) induced hypothermia and decreased locomotion in D2(+/+) mice, but had no effects in D2(-/-) mice; the magnitude of the hypothermic and locomotor-reducing effects of these two agonists in D2(+/+) mutants was approximately half that of D2(+/+) mice [31].
  • In the present study, quantitative autoradiography was used to examine the binding of [(3)H]SCH 23390, [(3)H]raclopride and [(3)H]7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin) to dopamine D1, D2, and D3 receptors, respectively, in various brain regions of ci3 rats and unaffected rats of the background strain (BH.7A(LEW)/Won) [32].
  • Using the quantitative microdialysis 'point of no net flux' method, we estimated the interstitial free concentration (IFC) of (+/-)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT) in the dorsal striatum of freely moving rats after i.p. administration of the drug at the dose of 18.3 mumol/kg [33].
  • Effects of (-)eticlopride and 7-OH-DPAT on the tail-suspension test in mice [34].


  1. S33084, a novel, potent, selective, and competitive antagonist at dopamine D(3)-receptors: II. Functional and behavioral profile compared with GR218,231 and L741,626. Millan, M.J., Dekeyne, A., Rivet, J.M., Dubuffet, T., Lavielle, G., Brocco, M. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  2. Mechanisms and sites of ocular action of 7-hydroxy-2-dipropylaminotetralin: a dopamine(3) receptor agonist. Chu, E., Chu, T.C., Potter, D.E. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  3. Involvement of dopamine D3 receptors in the area postrema in R(+)-7-OH-DPAT-induced emesis in the ferret. Yoshikawa, T., Yoshida, N., Hosoki, K. Eur. J. Pharmacol. (1996) [Pubmed]
  4. Effects of putative dopamine D3 receptor agonists, 7-OH-DPAT, and quinpirole, on yawning, stereotypy, and body temperature in rats. Kurashima, M., Yamada, K., Nagashima, M., Shirakawa, K., Furukawa, T. Pharmacol. Biochem. Behav. (1995) [Pubmed]
  5. Additive hypothermic effects of the 5-HT1A receptor agonist 8-OH-DPAT and the dopamine D2/3 receptor agonist 7-OH-DPAT in the rat. Eltayb, A., Lindblom, S., Oerther, S., Ahlenius, S. Acta Physiol. Scand. (2001) [Pubmed]
  6. Differential effects of 7-OH-DPAT and apomorphine on hyperactivity induced by MK-801 (dizocilpine) in rats. Clements, R.L., Greenshaw, A.J. Neuropharmacology (2005) [Pubmed]
  7. Local administration of dopaminergic drugs into the ventral tegmental area modulates cataplexy in the narcoleptic canine. Reid, M.S., Tafti, M., Nishino, S., Sampathkumaran, R., Siegel, J.M., Mignot, E. Brain Res. (1996) [Pubmed]
  8. The dopamine receptor agonist 7-OH-DPAT modulates the acquisition and expression of morphine-induced place preference. Rodríguez De Fonseca, F., Rubio, P., Martín-Calderón, J.L., Caine, S.B., Koob, G.F., Navarro, M. Eur. J. Pharmacol. (1995) [Pubmed]
  9. Investigations into the nature of a 7-OH-DPAT discriminative cue: comparison with D-amphetamine. Varty, G.B., Higgins, G.A. Eur. J. Pharmacol. (1997) [Pubmed]
  10. The putative dopamine D3 agonist, 7-OH-DPAT, reduces dopamine release in the nucleus accumbens and electrical self-stimulation to the ventral tegmentum. Gilbert, D.B., Millar, J., Cooper, S.J. Brain Res. (1995) [Pubmed]
  11. Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Caine, S.B., Koob, G.F. Science (1993) [Pubmed]
  12. Psychostimulant-induced Fos protein expression in the thalamic paraventricular nucleus. Deutch, A.Y., Bubser, M., Young, C.D. J. Neurosci. (1998) [Pubmed]
  13. Dopamine D(3) receptors and salt-dependent hypertension. Luippold, G., Zimmermann, C., Mai, M., Kloor, D., Starck, D., Gross, G., Mühlbauer, B. J. Am. Soc. Nephrol. (2001) [Pubmed]
  14. Gialpha3 protein-coupled dopamine D3 receptor-mediated inhibition of renal NHE3 activity in SHR proximal tubular cells is a PLC-PKC-mediated event. Pedrosa, R., Gomes, P., Hopfer, U., Jose, P.A., Soares-da-Silva, P. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  15. 7-OH-DPAT and PD 128907 selectively activate the D3 dopamine receptor in a novel environment. Pritchard, L.M., Logue, A.D., Hayes, S., Welge, J.A., Xu, M., Zhang, J., Berger, S.P., Richtand, N.M. Neuropsychopharmacology (2003) [Pubmed]
  16. Bromocriptine and quinpirole, but not 7-OH-DPAT or SKF 38393, potentiate the inhibitory effect of L-NAME on ethanol-induced locomotor activity in mice. Uzbay, I.T., Kayir, H. Naunyn Schmiedebergs Arch. Pharmacol. (2003) [Pubmed]
  17. Independent roles of dopamine D1 and D2/3 receptors in rat thermoregulation. Salmi, P. Brain Res. (1998) [Pubmed]
  18. Postglomerular vasoconstriction induced by dopamine D(3) receptor activation in anesthetized rats. Luippold, G., Schneider, S., Vallon, V., Osswald, H., Mühlbauer, B. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  19. Behavioral effects induced by the dopamine D3 agonist 7-OH-DPAT in sexually-active and -inactive male rats. Ferrari, F., Giuliani, D. Neuropharmacology (1996) [Pubmed]
  20. The dopamine D3/2 agonist 7-OH-DPAT attenuates the development of morphine tolerance but not physical dependence in rats. Cook, C.D., Barrett, A.C., Syvanthong, C., Picker, M.J. Psychopharmacology (Berl.) (2000) [Pubmed]
  21. Increased levels of proneurotensin/neuromedin N mRNA in rat striatum and nucleus accumbens induced by 7-OH-DPAT and nafadotride. Levant, B., Garimelli, B., Shafer, R.A., Merchant, K.M. Neuropsychopharmacology (1999) [Pubmed]
  22. Differential regulation of dopamine D2 and D3 receptors by chronic drug treatments. Stanwood, G.D., Lucki, I., McGonigle, P. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  23. D2 dopamine receptors and modulation of spontaneous acetylcholine (ACh) release from rat striatal synaptosomes. Clos, M.V., García-Sanz, A., Vivas, N.M., Badia, A. Br. J. Pharmacol. (1997) [Pubmed]
  24. Presynaptic dopamine autoreceptors control tyrosine hydroxylase activation in depolarized striatal dopaminergic terminals. el Mestikawy, S., Glowinski, J., Hamon, M. J. Neurochem. (1986) [Pubmed]
  25. C1- and C3-methyl-substituted derivatives of 7-hydroxy-2-(di-n-propylamino)tetralin: activities at central dopamine receptors. Johansson, A.M., Nilsson, J.L., Karlén, A., Hacksell, U., Sanchez, D., Svensson, K., Hjorth, S., Carlsson, A., Sundell, S., Kenne, L. J. Med. Chem. (1987) [Pubmed]
  26. Discriminative stimulus properties of the dopamine D3 receptor agonists, PD128,907 and 7-OH-DPAT: a comparative characterization with novel ligands at D3 versus D2 receptors. Millan, M.J., Girardon, S., Monneyron, S., Dekeyne, A. Neuropharmacology (2000) [Pubmed]
  27. Interactions of (+)- and (-)-8- and 7-hydroxy-2-(di-n-propylamino)tetralin at human (h)D3, hD2 and h serotonin1A receptors and their modulation of the activity of serotoninergic and dopaminergic neurones in rats. Lejeune, F., Newman-Tancredi, A., Audinot, V., Millan, M.J. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  28. Characterization of the human dopamine D3 receptor expressed in transfected cell lines. MacKenzie, R.G., VanLeeuwen, D., Pugsley, T.A., Shih, Y.H., Demattos, S., Tang, L., Todd, R.D., O'Malley, K.L. Eur. J. Pharmacol. (1994) [Pubmed]
  29. Effects of selective serotonin and dopamine agonists on plasma levels of glucose, insulin and glucagon in the rat. Uvnäs-Moberg, K., Ahlenius, S., Alster, P., Hillegaart, V. Neuroendocrinology (1996) [Pubmed]
  30. Biphasic effects of D3-receptor agonists, 7-OH-DPAT and PD128907, on the D1-receptor agonist-induced hyperactivity in mice. Mori, T., Murase, K., Tanaka, J., Ichimaru, Y. Jpn. J. Pharmacol. (1997) [Pubmed]
  31. Dopamine D2 receptor knock-out mice are insensitive to the hypolocomotor and hypothermic effects of dopamine D2/D3 receptor agonists. Boulay, D., Depoortere, R., Perrault, G., Borrelli, E., Sanger, D.J. Neuropharmacology (1999) [Pubmed]
  32. Alterations in dopamine D3 receptors in the circling (ci3) rat mutant. Schirmer, M., Nobrega, J.N., Harrison, S.J., Löscher, W. Neuroscience (2007) [Pubmed]
  33. Estimation of the interstitial free concentration of the putative dopamine D3 receptor selective agonist 7-OH-DPAT in the dorsal striatum of freely moving rats. Gainetdinov, R.R., Sotnikova, T.D., Grekhova, T.V., Rayevsky, K.S. Neurosci. Lett. (1995) [Pubmed]
  34. Effects of (-)eticlopride and 7-OH-DPAT on the tail-suspension test in mice. Ferrari, F., Giuliani, D. J. Psychopharmacol. (Oxford) (1997) [Pubmed]
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