Towards a new generation of potential antipsychotic agents combining D 2 and 5-HT1A receptor activities

Journal of Medicinal Chemistry

Volumn 50, Issue 4, 2007, Pages 865-876

  Cuisiat, Stephane ^a,b   Bourdiol, Nathalie ^a,b   Lacharme, Vincent ^a,b   Newman Tancredi, Adrian ^a,c   Colpaert, Francis ^a,d   Vacher, Bernard ^a,b  

^a INSTITUT DE RECHERCHE PIERRE FABRE   (France)

^b Medicinal Chemistry 1 Division   (France)

^c Neurobiology 2 Division

^d Toulouse ISTMT 2 ^*  (France)

Author keywords

[No Author keywords available]

Indexed keywords

2 DIPROPYLAMINO 8 HYDROXYTETRALIN; BENZYLAMINE DERIVATIVE; DIHYDROBENZOFURAN DERIVATIVE; DOPAMINE 2 RECEPTOR; DOPAMINE 2 RECEPTOR BLOCKING AGENT; METHYLPHENIDATE; N [(2,2 DIMETHYL 2,3 DIHYDROBENZOFURAN 7 YLOXY)ETHYL] 3 (CYCLOPENT 1 ENYL)BENZYLAMINE; NEUROLEPTIC AGENT; SEROTONIN 1A AGONIST; SEROTONIN 1A RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL BEHAVIOR; ARTICLE; CHEMICAL REACTION; DRUG ACTIVITY; DRUG EFFECT; DRUG EFFICACY; DRUG INDICATION; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; HUMAN; HUMAN CELL; PSYCHOSIS; RECEPTOR AFFINITY; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN; ANIMALS; ANTIPSYCHOTIC AGENTS; BEHAVIOR, ANIMAL; BENZOFURANS; BENZYLAMINES; HELA CELLS; HUMANS; RADIOLIGAND ASSAY; RATS; RECEPTOR, SEROTONIN, 5-HT1A; RECEPTORS, DOPAMINE D2; SIGNAL TRANSDUCTION; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33847354629     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm061180b     Document Type: Article

References (92)

1. Lublin, H.; Eberhard, J.; Levander, S. Current therapy issues and unmet clinical needs in the treatment of schizophrenia: A review of the new generation antipsychotics. Int. Clin. Psychopharmacol. 2005, 20(4), 183-198.
2. Seeman, P.; Lee, T.; Chau-Wong, M.; Wong, K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976, 261, 717-719.
3. Creese, I.; Burt, D. R.; Snyder, S. H. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 1976, 192, 481-483.
4. Crow, T. J.; Johnstone, E. C.; Deakin, J. F.; Longden, A. Dopamine and schizophrenia. Lancet 1976. 2, 563-566.
5. Johnstone, E. C.; Crow, T. J.; Frith, C. D.; Carney, M. W.; Price, J. S. Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet 1978, 1, 848-851.
6. Seeman, P. Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1987, 1, 133-152.
7. Casey, D. E. Motor and mental aspects of extrapyramidal syndromes. Int. Clin. Psychopharmacol. 1995, 10 (S3), 105-114.
8. Wieck, A.; Haddad, P. Hyperprolactinaemia caused by antipsychotic drugs. BMJ 2002, 324, 250-252.
9. Meltzer, H. Y.; Matsubaras, S.; Lee, J.-C. The ratios of serotonin-2 and dopamine-2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol. Bull. 1989, 25, 390-392.
10. Davis, J. M.; Chen, N.; Glick, I. D. A meta-analysis of the efficacy of second-generation antipsychotics. Arch. Gen. Psychiatry 2003, 60, 553-564.
11. Geddes, J.; Freemantle, N.; Harrison, P.; Bebbington, P. Atypical antipsychotics in the treatment of schizophrenia: Systematic overview and meta-regression analysis. BMJ 2000, 321, 1371-1376.
12. Leucht, S.; Barnes, T. R. E.; Kissling, W.; Engel, R. R.; Correll, C.; Kane, J. M. Relapse prevention in schizophrenia with new-generation antipsychotics: A systematic review and exploratory meta-analysis of randomized, controlled trials. Am. J. Psychiatry 2003, 160, 1209-1222.
13. Lieberman, J. A. Dopamine partial agonists: A new class of antipsychotic. CNS Drugs 2004, 18, 251-267.
14. Cosi, C.; Carilla-Durand, E.; Assie, M. B.; Ormiere, A. M.; Maraval, M.; Leduc, N.; Newman-Tancredi, A. Partial agonist of the antipsychotics SSR181507, aripiprazole and bifeprunox at dopamine D2 receptors: G-protein activation and prolactin release. Eur. J. Pharmacol. 2006, 535, 135-144.
15. See also: El-Sayeh, H. G.; Morganti, C.; Adams, C. E. Aripiprazole for schizophrenia. Br. J. Psychiatry 2006, 189, 102-108.
16. Invernizzi, R. W.; Cervo, L.; Samanin, R. 8-Hydroxy-2-(di-N- propylamino) tetralin, a selective serotonin1A receptor agonist, blocks haloperidol-induced catalepsy by an action on raphe nuclei medianus and dorsalis. Neuropharmacology 1988, 27, 515-518.
17. 2 receptor antagonism with potent serotonin reuptake inhibition. J. Med. Chem. 2005, 48, 6855-6869.
18. Newman-Tancredi, A.; Assié, M. B.; Leduc, N.; Ormière, A-M.; Danty, N.; Cosi, C. Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia. Int. J. Neuropsychopharmacol. 2005, 8, 341-356.
19. Assié, M. B.; Ravailhe, V.; Faucillon, V.; Newman-Tancredi, A. Contrasting contribution of 5-HT1A receptor activation to neurochemical profile of novel antipsychotics: Frontocortical dopamine and hippocampal serotonin release in rat brain. J. Pharmacol. Exp. Ther. 2005, 315, 265-272.
20. Bruins Slot, L. A.; De Vries, L.; Newman-Tancredi, A.; Cussac, D. Differential profile of antipsychotics at serotonin 5-HT1A and dopamine D2S receptors coupled to extracellular signal-regulated kinase. Eur. J. Pharmacol. 2006, 534, 63-70.
21. (a) Bruins Slot, L. A.; Kleven, M. S.; Newman-Tancredi, A. Effects of novel antipsychotics with mixed D2 antagonist/5-HT1A agonist properties on PCP-induced social interaction deficits in the rat. Neuropharmacology 2005, 49, 996-1006.
22. (b) Kleven, M. S.; Barret-Grévoz, C.; Bruins Slot, L. A.; Newman-Tancredi, A. Novel antipsychotic agents with 5-HT1A agonist properties: Role of 5-HT1A receptor activation in attenuation of catalepsy induction in rats. Neuropharmacology 2005, 49, 135-143.
23. Bantick, R. A.; Deakin, J. F. W.; Grasby, P. M. The 5-HT1A receptor in schizophrenia: A promising target for novel atypical neuroleptics? J. Psychopharmacol. 2001, 15, 37-46.
24. Kapur, S.; Zipursky, R.; Jones, C.; Remington, G.; Houle, S. Relationship between dopamine D2 occupancy, clinical response, and side effects: A double-blind PET study of first-episode schizophrenia. Am. J. Psychiatry 2000, 157, 514-520.
25. 1A receptor activation and anti-cataleptic effects: High-efficacy agonists maximally inhibit haloperidol-induced catalepsy. Eur. J. Pharmacol. 2002, 453, 217-221.
26. (b) Rats were challenged with 0.63 mg/kg of s.c. haloperidol (4-(4-(p-chlorophenyl)-4-hydroxypiperidino)-4′-fluorobutyrophenone, [52-86-8]).
27. 8-Hydroxy-2-dipropylaminotetralin, [76135-31-4].
28. 1A receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential. Eur. J. Pharmacol. 2001, 420, 103-112.
29. 1A receptor agonist potential antipsychotic drug. Neuropsychopharmacology 2006, 31, 1-17.
30. (a) Vacher, B.; Cuisiat, S.; Koek, W.; Colpaert, F. Pierre Fahre Medicament, 3-(cyclopenten-1-yl)-benzyl or 3-(cyclopenten-1-yl)- heteroarylmethylamine derivatives and use thereof as medicines for treating schizophrenia. WO 04/035561, April 29, 2004.
31. Vacher, B.; Cuisiat, S.; Koek, W. Pierre Fahre Medicament novel 3-alkoxybenzylamine derivatives and their use as medicines for treating schizophrenia. WO 00/32557, June 8, 2000.
32. (b) Vacher, B.; Cuisiat, S.; Koek, W. Pierre Fabre Medicament novel [(2-substituted-5-thien-3-yl)-benzyl]-[2-([2-isopropoxy-5-fluoro]-phenoxy) -ethyl]-amine derivatives, method for the production and use thereof as medicaments. WO 00/58282, October 5, 2000.
33. See also: Wolin, R. L.; Santillan, A., Jr.; Tang, L.; Huang, C.; Jiang, X.; Lovenberg, T. W. Inhibitors of the glycine transporter type-2 (GlyT-2): Synthesis and biological activity of benzoylpiperidine derivatives. Bioorg. Med. Chem. 2004, 12, 4511-4532.
34. 1A and serotonin transporter affinity within a class of N- aryloxyethylindolylalkylamines. J. Med. Chem. 2004, 47, 3823-3842.
35. Mewshaw, R. E.; Husbands, M.; Gildersleeve, E. S.; Webb, M. B.; Shi, X.; Mazandarani, H.; Cockett, M. I.; Ochalski, R.; Brennan, J. A.; Abou-Gharbia, M.; Marquis, K.; McGaughey, G. B.; Coupet, J.; Andree, T. H. New generation dopaminergic agents. 2. Discovery of 3-OH-phenoxyethylamine and 3-OH-N1-phenylpiperazine dopaminergic template. Bioorg. Med. Chem. Lett. 1998, 8, 295-300.
36. Stanciuc, O.; Balaban, A. T. Reaction of pyrylium salts with nucleophiles. 23: triarylethene derivatives containing an oxyalkyleneamino or oxyalkylene-N-pyridinium side chain. J. Pharm. Sci. 1993, 82, 927-33.
37. Larock, R. C.; Gong, W. H.; Baker, B. E. improved procedures for the palladium-catalyzed intermolecular arylation of cyclic alkenes. Tetrahedron Lett. 1989, 30, 2603-2606.
38. Andrieux, J.; Barton, D. H. R.; Patin, H. Rhodium-catalyzed isomerisation of some unsaturated organic substrates. J. Chem. Soc., Perkin Trans. 1 1977, 359-363.
39. Ornstein, P. L.; Bleisch, T. J.; Arnold, M. B.; Wright, R. A.; Johnson, B. G.; Tizzano, J. P.; Helton, D. R.; Kallman, M. J.; Schoepp, D. D.; Herin, M. Substituted (2SR)-2-((1SR,2SR)-2-carboxycycloprop-1-yl) glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 2. Effects of aromatic substitution, pharmacological characterization, and bioavailability. J. Med. Chem. 1998, 41, 358-378.
40. Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L. S. On the nature of the "copper effect" in the Stille cross-coupling. J. Org. Chem. 1994, 59, 5905-5911.
41. Denmark, S. E.; Edwards, J. P. A Comparison of (chloromethyl)- and (iodomethyl)zinc cyclopropanation reagents. J. Org. Chem. 1991, 56, 6974-6981.
42. Malm, J.; Rehn, B.; Hörnfeldt, A.-B.; Gronowitz, S. Synthesis and NMR spectra of the six isomeric thieno[c]-fused 1,7- and 1,8-naphthyridines. J. Heterocycl. Chem. 1994, 31, 11-15.
43. 2-catalyzed Suzuki coupling reactions of aryl bromides under mild aerobic conditions. J. Org. Chem. 2004, 69, 4330-4335.
44. (a) Kabalka, G. W.; Namboodiri, V.; Wang, L. Suzuki coupling with ligand-less palladium and potassium fluoride. Chem. Commun. 2001, 8, 775.
45. (b) Demir, A. S.; Reis, O.; Emrullahoglu, M. Generation of aryl radicals from arylboronic acids by manganese(III) acetate: Synthesis of biaryls and heterobiaryls. J. Org. Chem. 2003, 68, 578-580.
46. Jordan, A. D.; Orsini, M. J.; Middleton, S. A.; Connolly, P. J.; Brenneman, D. E.; Pan, K.; Reitz, A. B. 8-(Heteroaryl)phenalkyl-1-phenyl-1,3,8- triazaspiro[4.5]decan-4-ones as opioid receptor modulators. Med. Chem. 2005, 1, 601-610.
47. Plummer, E. L. Pyrethroid insecticides derived from [1,1′-biphenyl] -3-methanol. 2. Heteroaromatic analogues. J. Agric. Food Chem. 1983, 31, 718-21.
48. Ackerley, N.; Brewster, A. G.; Brown, G. R.; Clarke, D. S.; Foubister, A. J.; Griffin, S. J.; Hudson, J. A.; Smithers, M. J.; Whittamore, P. R. O. A novel approach to dual-acting thromboxane receptor antagonist/synthase inhibitors based the link of 1,3-dioxane-thromboxane receptor antagonists and thromboxane synthase inhibitors. J. Med. Chem. 1995, 38, 1608-1628.
49. Canonne, P.; Bélanger, D.; Lemay, G. Steric effects in the reaction of di(bromomagnesio)alkanes with carboxylic esters. Tetrahedron Lett. 1981, 22, 4995-4998.
50. Cai, D.; Larsen, R. D.; Reider, P. J. Effective lithiation of 3-bromopyridine: synthesis of 3-pyridine boronic acid and variously 3-subtituted pyridines. Tetrahedron Lett. 2002, 43, 4285-4287.
51. McIntyre, J. A.; Castaner, J.; Bayes, M. Sarizotan hydrochloride. Antidyskinetic drug 5-HT(1A) receptor agonist dopamine D2 receptor ligand. Drugs Future 2006, 31, 314-319.
52. Sorbera, L. A.; Castaner, J. Bifeprunox mesylate. Drugs Future 2005, 30, 992-997.
53. Thurkauf, A.; Yuan, J.; Chen, X.; Wasley, J. W. F.; Paneitz, G.; Meade, R.; Woodruff, K. H.; Huston, K.; Ross, P. C. 3-Aminomethylbiphenyls. A new class of dopamine receptor ligands. Med. Chem. Res. 1996, 6, 69-80.
54. Thurkauf, A.; Yuan, J.; Chen, X.; Wasley, J. W.; Meade, R.; Woodruff, K. H.; Huston, K.; Ross, P. C. 1-Phenyl-3-(aminomethyl)pyrroles as potential antipsychotic agents: Synthesis and dopamine receptor binding. J. Med. Chem. 1995, 38, 4950-4952.
55. van Wijngaarden, I.; Kruse C. G.; van Hes, R.; van der Heyden, J. A.; Tulp, M. T. M. 2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 1. J. Med. Chem. 1987, 30, 2099-2104.
56. van Wijngaarden, I.; Kruse, C. G.; van der Heyden, J. A. M.; Tulp, M. T. M. 2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 2. J. Med. Chem. 1988, 31, 1934-1940.
57. 2 partial agonists: Mewshaw, R. E.; Zhao, R.; Shi, X.; Marquis, K.; Brennan, J. A.; Mazandarani, H.; Coupet, J.; Andree, T. H. New generation dopaminergic agents. Part 8: Heterocyclic bioisosteres that exploit the 7-OH-2-(aminomethyl)-chroman D(2) template. Bioorg. Med. Chem. Lett. 2002, 12, 271-274.
58. As D4 partial agonists: Arit, M.; Böttcher, H.; Riethmüller, A.; Schneider, G.; Bartoszyk, G. D.; Greiner, H.; Seyfried, C. A. SAR of novel biarylmethylamine dopamine D4 receptor ligands. Bioorg. Med. Chem. Lett. 1998, 8, 2033-2038.
59. Bergauer, M.; Hübner, H.; Gmeiner, P. 2,4-Disubstituted pyrroles: Synthesis, traceless linking and pharmacological investigations leading to the dopamine D4 receptor partial agonist FAUC 356. Bioorg. Med. Chem. Lett. 2002, 12, 1937-1940.
60. See also: Feenstra, R. W.; de Moes, J.; Hofma, J. J.; Kling, H.; Kuipers, W.; Long, S. K.; Tulp, M. T. M.; van der Heyden, J. A. M.; Kruse, C. G. New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsyehotics sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities. Bioorg. Med. Chem. Lett. 2001, 11, 2345-2349.
61. 1A subtype. We, therefore, orientated our efforts towards ortho- alkoxyphenoxyethylamino groups.
62. (b) See ref 17a.b. See also: Evrard, D. A.; Zhou, P.; Yi, S. Y.; Zhou, D.; Smith, D. L.; Sullivan, K. M.; Hornby, G. A.; Schechter, L. E.; Andree, T. H.; Mewshaw, R. E. Studies towards the next generation of antidepressants. Part 4: Derivatives of 4-(5-fluoro-1H-indol-3-yl)cyclohexylamine with affinity for the serotonin transporter and the 5-HT(1A) receptor. Bioorg. Med. Chem. Lett. 2005, 15, 911-914.
63. 1A receptor ligands (e.g., Société de Conseils de Recherches et d'Application Phenoxyethylamine derivatives having high affinity for the 5-HT1A receptor, process for their preparation, their use as drugs, and pharmaceutical compositions containing them. WO 9631461, 10 September, 1996).
64. 1A agonist properties: receptorial and neurochemical profile in comparison with clozapine and haloperidol. J. Pharmacol. Exp. Ther. 1998, 286, 1341-1355.
65. 1A receptors.
66. 2 receptors are given in Supporting Information.
67. 2L receptors coupled to GIRK potassium channels. Neuropharmacology 2007, in press.
68. (a) Koek, W.; Colpaert, F. C. Inhibition of methylphenidate-induced behaviors in rats: Differences among neuroleptics. J. Pharmacol. Exp. Ther. 1993, 267, 181-191.
69. (b) Prinssen, E. P. M.; Kleven, M.; Koek, W. The cataleptogenic effects of the neuroleptic nemonapride are attenuated by its 5-HT1A receptor agonist properties. Eur. J. Pharmacol. 1998, 356, 189-192.
70. Kleven, M.; Prinssen, E. P. M.; Koek, W. Role of 5-HT-1A receptors in the ability of mixed 5-HT-1A receptor agonist/dopamine D-2 receptor antagonists to inhibit methylphenidate-induced behaviors in rats. Eur. J. Pharmacol. 1996, 313, 25-34.
71. The cataleptogenic effect was measured by the latency to recover from an unusual posture, that is, crossed-legs position according to: Kleven, M. S.; Barret-Grevoz, C.; Bruins-Slot, L.; Newman-Tancredi, A. Novel antipsychotic agents with 5-HT1A agonist properties: Role of 5-HT1A receptor activation in attenuation of catalepsy induction in rats. Neuropharmacology 2005, 49, 135-143.
72. See also: Bardin, L.; Kleven, M.; Barret-Grevoz, C.; Depoortere, R.; Newman-Tancredi, A. Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. Neuropsychopharmacology 2006, 31, 1869-1879.
73. 2 dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Br. J. Psychiatry 2001, 179, 503-508.
74. 2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behaviour in rats. Psychopharmacology 2000, 150, 422-429.
75. Kleven, M.; Prinssen, E. P. M.; Koek, W. Eur. J. Pharmacol. 1996, 313, 25-34.
76. Prinssen, E. P. M.; Koek, W.; Kleven, M. Effects of WAY 100635 on antipsychotic-induced catalepsy in 5-HT depleted animals: A role for tonic activation of 5-HT1A receptors. Eur. J. Pharmacol. 2000, 395, 143-147.
77. Wadenberg, M.-L. G.; Young, K. A.; Richter, J. T.; Hicks, P. B. Effects of local application of 5-hydroxytryptamine into the dorsal or median raphe nuclei on haloperidol-induced catalepsy in the rat. Neuropharmacology 1999, 38, 151-156.
78. Leucht, S.; Wahlbeck, K.; Hamann, J.; Kissling, W. New generation antipsychotics versus low-potency conventional antipsychotics: A systematic review and meta-analysis. Lancet 2003, 361, 1581-1589.
79. 1A actions.
80. Tricklebank, M. D.; Forler, C.; Fozard, J. R. The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioral response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. Eur. J. Pharmacol. 1984, 106, 271-282.
81. Forepaw treading (FPT) was also examined. Because compound 16 did not produced any FPT even at the highest dose tested i.p. (40 mg/kg), FPT is not reported in Table 3.
82. 1A subtypes, pharmacokinetics, metabolite(s), and so on) could alter the results presented in this paper.
83. 2 receptor blockade. Neuropsychopharmacology 2006, 31, 1900-1909.
84. Depoortere, R.; Auclair, A.; Bardin, L.; Bruins-Slot, L.; Kleven, M. S.; Newman-Tancredi, A. F15063, a potential antipsychotic with D2/D3 antagonist, 5-HT1A agonist and D4 partial agonist properties: III) Profile in tests predictive of activity against cognitive deficits and negative symptoms of schizophrenia. Br. J. Pharmacology 2007, in press.
85. Bardin, L.; Auclair, A.; Kleven, M. S.; Prinssen, E.; Koek, W.; Newman-Tancredi, A.; Depoortere, R. Pharmacological profiles in rats of novel antipsychotics with combined dopamine D2/serotonin 5-HT1A activity: Comparison with conventional antipsychotics. Psychopharmacology 2007, in press.
86. Newman-Tancredi, A.; Assié, M. B.; Leduc, N.; Ormière, A.-M.; Danty, N.; Cosi, C. Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: Affinity, efficacy and potential implications for treatment of schizophrenia. Int. J. Neuropsychopharmacol. 2005, 8, 341-356.
87. Kleven, M. S.; Assié, M. B.; Koek, W. Pharmacological characterization of in vivo properties of putative mixed 5-HT(1A) agonist/5-HT(2A/2C) antagonist anxiolytics. II. Drug discrimination and behavioral observation studies in rats. J. Pharmacol. Exp. Ther. 1997, 282, 747-759.
88. McPherson, G. A. Analysis of radioligand binding experiments. A collection of computer programs for the IBM PC. J. Pharmacol. Methods 1985, 14, 213-228.
89. Cosi, C.; Koek, W. The putative [dlt]silent[dmt] 5-HT(1A) receptor antagonist, WAY 100635, has inverse agonist properties at cloned human 5-HT(1A) receptors. Eur. J. Pharmacol. 2000, 401, 9-15.
90. See also: Cosi, C.; Koek, W. Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT(1A) receptors expressed in HeLa cells. Eur. J. Pharmacol. 2001, 433, 55-62.
91. Colpaert, F. C.; Koek, W.; Lehmann, J.; Rivet, J. M.; Lejeune, F.; Canton, H.; Bervoets, K.; Millan, M. J.; Laubie, M.; Lavielle, G. S 14506: A novel, potent, high-efficacy 5-HT(1A) agonist and potential anxiolytic agent. Drug Dev. Res. 1992, 26, 21-48.
92. Tallarida, R. J.; Murray, R. B. Manual of Pharmacologic Calculations with Computer Programs, 2nd edition; Springer-Verlag: New York, 1987.