FG5893: A potential new generation anxiolytic/antidepressant drug with high affinity for 5-HT1A and 5-HT2A receptors

CNS Drug Reviews

Volumn 2, Issue 4, 1996, Pages 363-383

  Andersson, Gunnar ^a   Albinsson, Agneta ^a   Björk, Anders ^a   Svartengren, Jan ^a  

^a Pharmacia & Upjohn AB   (Sweden)

Author keywords

5 HT1A receptor agonists; 5 HT2A receptor antagonists; Anxiety; Depression; FG5893; Pharmacology

Indexed keywords

2 DIPROPYLAMINO 8 HYDROXYTETRALIN; AMPEROZIDE; ANXIOLYTIC AGENT; BUSPIRONE; CORTICOSTERONE; FG 5893; IPSAPIRONE; RITANSERIN; SEROTONIN 1A RECEPTOR; SEROTONIN 2A RECEPTOR; UNCLASSIFIED DRUG;

AGGRESSION; ALCOHOL CONSUMPTION; ANIMAL BEHAVIOR; ANXIETY; ARTICLE; CORE TEMPERATURE; CORTICOSTERONE BLOOD LEVEL; DEPRESSION; DOSE RESPONSE; DRUG ANALYSIS; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HEAD TWITCH; IMMOBILIZATION; INTRAPERITONEAL DRUG ADMINISTRATION; LOCOMOTION; NONHUMAN; ORAL DRUG ADMINISTRATION; PASSIVE AVOIDANCE; SEXUAL BEHAVIOR; SUBCUTANEOUS DRUG ADMINISTRATION; TRANQUILIZING ACTIVITY;

EID: 0030438097     PISSN: 1080563X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1527-3458.1996.tb00307.x     Document Type: Article

References (130)

1. Abou-Gharbia M, Moyer JA. Wy-50, 324. Drugs Future 1990;15:1093-1094.
2. Aghajanian GK, Sprouse JS, Rasmussen K. Physiology of midbrain serotonin systems. In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress. New York: Raven Press, 1987:141-149.
3. Ahlenius S, Eriksson H, Larsson K, Modigh K, Södersten P. Mating behavior in the male rat treated with p-chlorophenylalanine methyl ester alone and in combination with pargyline. Psychopharmacologia (Berl.) 1971;20:383-388.
4. Ahlenius S, Larsson K. Effects of the putative 5-HT agonist 5-OH-DPAC on male rat sexual behaviour: A comparison with effects produced by 8-OH-DPAT and buspirone. J Psychopharmacol 1988;2:47-53.
5. 3 Antagonists, and Benzodiazepines: Their Comparative Behavioural Pharmacology. Chichester: John Wiley & Sons Ltd, 1991:281-315.
6. 1A Receptors. Chichester: Ellis Horwood, 1987:185-198.
7. Ahlenius S, Larsson K, Svensson L. Further evidence for an inhibitory role of central 5-HT in male rat sexual behavior. Psychopharmacology 1980;68:217-220.
8. Ahlenius S, Larsson K, Svensson L, et al. Effects of a new type of 5-HT receptor agonist on male rat sexual behavior. Pharmacol Biochem Behav 1981;15:785-792.
9. Albinsson A, Andersson G. The effect of amperozide, a new antipsychotic drug, on plasma corticosterone concentration in the rat. Life Sci 1992;51:1535-1544.
10. Albinsson A, Andersson G, Andersson K, Vega-Matuszczyk J, Larsson K. The effects of lesions in the mesencephalic raphe systems on male rat sexual behavior and locomotor activity. Behav Brain Res 1996;80:57-63.
11. 2A receptors. Eur J Pharmacol 1994;261:285-294.
12. 2 receptor in the 5-HT receptor-mediated stimulation of prolactin release. Eur J Pharmacol 1994;251:157-161.
13. 2 receptor antagonistic properties, on male rat sexual behavior. Eur J Pharmacol 1994;255:131-137.
14. Arvidsson L-E, Hacksell U, Nilsson JLG, et al. 8-Hydroxy-2-(di-n-propylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonist. J Med Chem 1981;24:921-923.
15. Barnett SA. The Rat: A Study in Behaviour. Chicago: The University of Chicago Press, 1975.
16. 3 Antagonists, and Benzodiazepines: Their Comparative Behavioural Pharmacology. Chichester: John Wiley & Sons Ltd, 1991:59-105.
17. 1C receptor mediated behaviour in rats following chronic treatment with 5-HT receptor agonists, antagonists, or anti-depressants. Psychopharmacology 1991;105:219-224.
18. 1A receptors induces lower lip retraction in the rat. Pharmacol Biochem Behav 1989;33:821-827.
19. Bill DJ, Knight M, Forster EA, Fletcher A. Direct evidence for an important species difference in the mechanism of 8-OH-DPAT-induced hypothermia. Br J Pharmacol 1991;103:1857-1864.
20. Björk A, Olsson NG, Christensson E, Martinsson K, Olsson O. Effects of amperozide on biting behaviour and performance in restricted-fed pigs following regrouping. J Anim Sci 1988;66:669-675.
21. Blundell JE. Serotonin and appetite. Neuropharmacology 1984;23:1537-1551.
22. Brocco MJ, Koek W, Degryse AD, Colpaert FC. Comparative studies on the antipunishment effects of chlordiazepoxide, buspirone, and ritanserin in the pigeon. Geller Seifer and Vogel conflict procedures. Behav Pharmacol 1990;1:403-418.
23. Carli M, Prontera C, Samanin R. Evidence that central 5-hydroxytryptaminergic neurones are involved in the anxiolytic activity of buspirone. Br J Pharmacol 1989;96:829-36.
24. Ceulemans DLS, Hoppenbrouwers MLJA, Gelders YG, Reyntjens AJM. The influence of ritanserin, a serotonin antagonist, in anxiety disorders: A double-blind placebo-controlled study versus lorazepam. Pharmacopsychiatry 1985;18:303-305.
25. Christensson E, Björk A. Amperozide: A new pharmacological approach in the treatment of schizophrenia. Pharmacol Toxicol (Suppl 1) 1990;5-7.
26. Collins D, Myers RD. Buspirone attenuates volitional alcohol intake in the chronically drinking monkey. Alcohol 1987;4:49-56.
27. Conn PJ, Sanders-Bush E. Biochemical characterization of serotonin stimulated phosphoinositide turnover. Life Sci 1986;38:663-669.
28. Conn PJ, Sanders-Bush E. Agonist induced phosphoinositide hydrolysis in choroid plexus. J Neurochem 1986;47:1754-1760.
29. Costall B, Naylor RJ, Cannon JG, Lee T. Differentiation of the dopamine mechanisms mediating stereotyped behaviour and hyperactivity in the nucleus accumbens and caudate-putamen. J Pharm Pharmac 1977;29:337-342.
30. Costall B, Naylor RJ, Marsden CD, Pycock CJ. Serotoninergic modulation of the dopamine response from the nucleus accumbens. J Pharm Pharmac 1976;28:523-526.
31. 2 receptors? Pharmacol Biochem Behav 1990;36:901-906.
32. Delini-Stula A, Vassout A. The effects of antidepressants on aggressiveness induced by social deprivation in mice. Pharmacol Biochem Behav 1981;14:33-41.
33. 1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig and rat hippocampal membranes. J Pharmacol Exp Ther 1986;238:248-253.
34. 2 receptors, depression and anxiety. Pharmacol Biochem Behav 1988;29:819-820.
35. 1A receptors in anxiety. In: Briley M, File SE, ed. New Concepts in Anxiety. London: MacMillan Press, 1991:94-129.
36. Di Chiara G, Camba R, Spano PF. Evidence for inhibition by brain serotonin of mouse killing behaviour in rats. Nature 1971;233:272-273.
37. Dourish CT, Hutson PH, Kennett GA, Curzon G. 8-OH-DPAT-induced hyperphagia: Its neural basis and possible therapeutic relevance. Appetite (Suppl) 1986;7:127-140.
38. Eison AS, Eison MS, Stanley M, Riblet LA. Serotonergic mechanisms in the behavioural effects of buspirone and gepirone. Pharmacol Biochem Behav 1986;24:701-707.
39. Fuller RW. Drugs influencing serotoninergic neurotransmission. In: Müller EE, ed. Neitroactive Drugs in Endocrinology. Elsevier/North-Holland Biomedical Press, 1980:123-135.
40. Fuller RW, Snoddy HD. Serotonin receptor subtypes involved in the elevation of serum corticosterone concentration in rats by direct- and indirect-acting serotonin agonists. Neuroendocrinology 1990;52:206-211.
41. Gammans RE, Mayol RF, Labuddle JA. Metabolism and disposition of buspirone. Am J Med 1986;80:41-51.
42. Garattini S, Valzelli L. Is the isolated animal a possible model for phobia and anxiety? Prog Neuropsychopharmacol 1981;5:159-165.
43. 1A receptor subtype increases rat plasma ACTH concentration. Eur J Pharmacol 1988;147:431-439.
44. Gill K, Amit Z. Serotonin uptake blockers and voluntary alcohol consumption. A review of recent studies. In: Galanter M, ed. Recent Developments in Alcoholism. New York: Plenum Press, 1989:225-248.
45. 1A receptor ligand with anxiolytic and antidepressant properties. Drugs Future 1988;13:429-439.
46. 1A Receptors. Chichester: Ellis Horwood, 1987:106-119.
47. Glennon RA, Darmani NA, Martin BR. Multiple populations of serotonin receptors may modulate the behavioral effects of serotonergic agents. Life Sci 1991;48:2493-2498.
48. Goa KL, Ward A. Buspirone: A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. Drugs 1986;32:114-129.
49. Gobbi M, Cavanus S, Miari A, Mennini T. Effect of acute and chronic administration of buspirone on serotonin and benzodiazepine receptor subtypes in the rat brain. Neuropharmacol 1991;30:313-321.
50. 1A receptor agonists and antagonists: A comparison to adrenergic and dopaminergic neurons in rats. J Pharmacol Exp Ther 1995;273:1032-1046.
51. 1A receptor function. Prog Neuropsychopharmacol Biol Psychiat 1989;13:445-51.
52. 2 receptors. Br J Pharmac 1985;84:743-753.
53. Green RA, Gillin JC, Wyatt RJ. The inhibitory effect of intraventricular administration of serotonin on spontaneous motor activity of rats. Psychopharmacology 1976;51:81-84.
54. 1A receptors. Neuropharmacology 1986;25:1307-1313.
55. Gustafsson B, Christensson E. Amperozide and emotional behaviour. Pharmacol Toxicol (suppl 1) 1990;66:34-39.
56. Hensman R, Guimaraes FS, Wang M, Deakin JFW. Effects of ritanserin on aversive classical conditioning in humans. Psychopharmacology 1991;104:220-224.
57. Heym J, Mena EE, Seymour PA. SM-3997: A non-benzodiazepine anxiolytic with potent and selective effects on serotonergic neurotransmission. Soc Neurosci Abstr 1987;13:127.
58. Hillegaart V. Effects of local application of 5-HT and 8-OH-DPAT into the dorsal and median raphe nuclei on motor activity in the rat. Physiol Behav 1990;48:143-148.
59. Hillegaart V, Ahlenius S, Larsson K. Region-selective inhibition of male rat sexual behavior and motor performance by localized forebrain 5-HT injections: A comparison with effects produced by 8-OH-DPAT. Behav Brain Res 1991;42:169-180.
60. Hjorth S, Carlsson A. Buspirone: Effects on central monoaminergic transmission - possible relevance to animal experimental and clinical findings. Eur J Pharmacol 1982;83:299-303.
61. Hjorth S, Carlsson A, Lindberg P, et al. 8-Hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity. J Neural Transm 1982;55:169-188.
62. 1A autoreceptor-mediated effects of the amperozide congeners, FG5865 and FG5893, on rat brain 5-hydroxytryptamine neurochemistry in vivo. Eur J Pharmacol 1993;238:357-367.
63. 1 recognition sites. J Receptor Res 1988;8:59-81.
64. Insel TR, Miller LP, Gelhard RE, Hill JL. Rat pup ultrasonic isolation calls and the benzodiazepine receptor. In: Newman JD, ed. The Physiological Control of Mammalian Vocalization. New York: Plenum Press, 1988:331.
65. Jacobs BL, Trimbach C, Eubanks EE, Trulson M. Hippocampal mediation of raphe lesion- and PCPA-induced hyperactivity in the rat. Brain Res 1975;94:253-261.
66. Janssen PAJ, Jageneau AH, Niemegeers CJE. Effects of various drugs on isolation-induced fighting of male mice. J Pharmacol Exp Ther 1960;129:471-475.
67. 1A receptors in the mediation of exploratory locomotor activity in the rat. J Psychopharmacol 1989;3:32-35.
68. 1A receptor agonists and in their inhibitory effects on the firing of serotonergic neurons in the rat? J Pharmacol Exp Ther 1995;272:920-929.
69. 1A receptor-mediated effects of buspirone, gepirone, and ipsapirone. Pharmacol Biochem Behav 1988;29:711-715.
70. Kuemmel B, Beneke M, Krol G, Schoellenhammer G, Spechtmeyer H. Ipsapirone in the treatment of generalized anxiety disorders: Results of a phase II vs. multicenter trial. Psychopharmacology (suppl) 1988;96:353.
71. Larsson K, Ahlenius S. Masculine sexual behavior and brain monoamines. Psychopharmacology 1985;87:15-32.
72. Larsson K, Fuxe K, Everitt BJ, Holmgren M, Södersten P. Sexual behavior in male rats after intracerebral injection of 5,7-dihydroxytryptamine. Brain Res 1978;141:293-303.
73. 1A receptor agonist 8-OH-DPAT. Neuropharmacology 1990;29:85-91.
74. Leysen JE. Gaps and peculiarities. Neuropsychopharmacology 1990;3:361-369.
75. 2 receptors, roles and regulation. The neuropharmacology of serotonin. Ann NY Acad Sci 1990;600:183-193.
76. Liposits ZS, Phelix C, Paull WK. Synaptic interaction of serotonergic axons and corticotrophin releasing factor (CRF) synthesizing neurons in the hypothalamic paraventricular nucleus of the rat. Histochemistry 1987;86:541-549.
77. 2) agonists and antagonists on renin and corticosterone secretion. Neuroendocrinology 1987;45:305-310.
78. Lucki E, Ward HR. Antagonism of serotonin-mediated behaviour in rats by pretreatment with the nonbenzodiazepine anxiolytics buspirone or ipsapirone. Soc Neurosci Abstr 1986;12:1236.
79. 1B serotonin receptor: Cloning, functional expression, and localization in motor control centers. Proc Natl Acad Sci USA 1992;89:3020-3024.
80. 1A postsynaptic receptors in the learned helplessness paradigm. Life Sci 1991;48:2505-2511
81. McBride W, Murphy J, Lumeng L, Li TK. Serotonin and ethanol preference: In: Galanter M, ed. Recent Developments in Alcoholism. New York: Plenum Press, 1989:187-209.
82. 1C/2 receptors. J Pharmacol Exp Ther 1992;262:451-463.
83. Mos J, Olivier B. Ultrasonic vocalizations by rat pups as an animal model for anxiolytic activity: Effects of serotonergic drugs. In: Bevan P, Cools AR, Archer T, eds. Behavioural Pharmacology of S-HT. Hillsdale, NJ: Lawrence Erlbaum, 1989:361-366.
84. Murphy JM, Waller MB, Gatto GJ, McBride WJ, Lumeng L, Li TK. Effects of fluoxetine on the intragastric self-administration of ethanol in the alcohol preferring P line of rats. Alcohol 1988;5:283-286.
85. Myers RD. Lankford M, Björk A. Selective reduction by the 5-HT antagonist amperozide of alcohol preference induced in rats by systemic cyanamide. Pharmacol Biochem Behav 1992;43:661-667.
86. 2 receptor blockade by amperozide suppresses ethanol drinking in genetically preferring rats. Pharmacol Biochem Behav 1993;45:741-747.
87. 2 antagonist amperozide. Alcohol 1993;10:117-125.
88. Myers RD, Melchior C. Alcohol and alcoholism: Role of serotonin. In: Essman W, ed. Serotonin in Health and Disease. New York: Spectrum, 1977:373-130.
89. Myers RD, Quarfordt S. Alcohol drinking attenuated by sertraline in rats with 6-OHDA or 5,7-DHT lesions of N. accumbens: A caloric response? Pharmacol Biochem Behav 1991;40:923-928.
90. 1A receptor activation. J Pharmacol 1992;106:603-609.
91. Oliver B, Mos J, Van der Heyden J, Hartog J. Serotonergic modulation of social interactions in isolated male mice. Psychopharmacology 1989;97:154-156.
92. Palacios JM, Waeber C, Hoyer D, Mengod G. Distribution of serotonin receptors. Ann NY Acad Sci 1990;600:36-52.
93. 3 receptor antagonists ICS 205-930 on the footshock-induced place aversion conditioning in rats. Eur J Pharmacol 1988;151:321-324.
94. 3 receptor antagonists ICS 205-930 and GR 38032F, putative anxiolytic drugs, differ from diazepam in their pharmacological profile. J Psychopharmacol 1989;3:14-20.
95. Pazos A, Crtes R, Palacios JM. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors. Brain Res 1985;346:231-249.
96. 3H]spiroperidol by chronic treatment with the antidepressant amitriptyline. J Pharmacol Exp Ther 1980;215:582-587.
97. Pettersson E. Studies of four novel diphenylbutylpiperazinepyridyl derivatives on release and inhibition of reuptake of dopamine, serotonin, and noradrenaline by rat brain in vitro. Eur J Pharmacol 1995;282:131-135.
98. Porsolt RD, Anton G, Blavet N, Jalfre M. Behaviour despair in rats: A new model sensitive to antidepressant treatment. Eur J Pharmacol 1978;47:379-391.
99. Privette TH, Hornsby RL, Myers RD. Buspirone alters alcohol drinking induced in rats by tetrahydropapaveroline injected into the brain monoaminergic pathways. Alcohol 1988;5:147-152.
100. 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat. Pharmacol Biochem Behav 1989;33:329-334.
101. Rényi L, Archer T, Minor GG, Tandberg B, Fredriksson A, Ross SB. The inhibition of the cage-leaving response - a model for studies of the serotonergic neurotransmission in the rat. J Neural Transm 1986;65:193-210.
102. 2-blocker. Drug Dev Res 1986;8:205-211.
103. 1C receptors. J Pharmacol Exp Ther 1992;260:1361-1365.
104. Rowan MJ, Cullen WK, Moulton B. Buspirone impairment of performance of passive avoidance and spatial hearing tasks in the rat. Psychopharmacology 1990;100:393-398.
105. Sanger DJ, Joly D, LePichon M. Buspirone, gepirone, and ipsapirone disrupt both active and passive avoidance responding in rats. Behav Pharmacol 1989;1:153-160.
106. Schlechter LE, Bolanos FJ, Gozlan H, et al. Alterations of central serotoninergic and dopaminergic neurotransmission in rats chronically treated with ipsapirone: Biochemical and electrophysiological studies. J Pharmacol Exp Ther 1990;255:1335-1347.
107. Schipper J, Tulp MThM, Berkelmans B, Mos J, Van der Heijden JAM, Olivier B. Preclinical pharmacology of flesinoxan: A potential anxiolytic and antidepressant drug. Human Psychopharmacol 1991;6:53-61.
108. 1A receptor agonists 8-OH-DPAT, ipsapirone and buspirone in the rat. Eur J Pharmacol 1993;249:341-351.
109. 1A autoreceptor function. In: Bradley PB, Cooper SJ, Handley SL, eds. 5-Hydroxytryptamine, CNS Receptors and Brain Function. New York: Pergamon Press, 1993:297.
110. 2 antagonist FG5893. Alcohol 1993;10:243-248.
111. 1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Eur J Neurosci 1990;2:1144-1154.
112. Stewart RM, Campbell A, Sperk G, Baldessarini RJ. Receptor mechanisms in increased sensitivity to serotonin agonists after dihydroxytryptamine shown by electronic monitoring of muscle twitches in the rat. Psychopharmacology 1979;60:281-289.
113. 2A receptors following chronic treatment with amperozide. J Receptor Res 1993;13:379-392.
114. Svensson L, Engel J, Hard E. Effect of the 5-HT receptor agonist 8-OH-DPAT on ethanol preference in the rat. Alcohol 1989;6:17-21.
115. Taylor DP. Serotonin agents in anxiety. Ann NY Acad Sci 1990;600:545-556.
116. Taylor M. Effects of L-tryptophan and L-methionine on activity in the rat. Br J Pharmacol 1976;58:117-119.
117. Traber J, Davoes MA, Dompert WV, Glaser T, Schuurman T, Seidel P-R. Brain serotonin receptors as a target for the putative anxiolytic TVX Q 7821. Brain Res Bull 1984;12:741-744.
118. 1A receptor. In: Dourish CD, Ahlenius S, Hutson PH, eds. Receptors: Behavioral and Neurochemical Pharmacology. Chichester: Ellis Horwood Ltd, 1987:140-151.
119. 1 receptor and catecholaminergic systems in the behavioral response to 8-hydro-2-(di-n-propylamino)tetralin in the rat. Eur J Pharmacol 1984;106:271-282.
120. Trulson ME, Eubanks EE, Jacobs BL. Behavioral evidence for supersensitivity following destruction of central serotonergic nerve terminals by 5,7-dihydroxytryptamine. J Pharmacol Exp Ther 1976;198:23-32.
121. Van Wijngaarden I, Tulp MT, Soudijin W. The concept of selectivity in 5-HT receptor research. Ew J Pharmacol 1990;188:301-312.
122. 1A-sensitive adenylyl cyclase of rodent hippocampal neurons: Effects of antidepressant treatments and chronic stimulation with agonists. J Pharmacol Exp Ther 1991;257:433-438.
123. Warbritton III JD, Stewart RM, Baldessarini RJ. Decreased locomotor activity and attenuation of amphetamine hyperactivity with intraventricular infusion of serotonin in the rat. Brain Res 1978;143:373-382.
124. 1Dβ. Proc Natl Acad Sci USA 1992;89:3630-3634.
125. 1A receptors in rat brain following long-term antidepressant drug treatment. Synapse 1989;4:347-352.
126. 1A agonists measured with the forced swim test. Psychopharmacology 1990;101:497-504.
127. Wirtshafter D, Asin KE. Evidence that electrolytic median raphe lesions increase locomotion but not exploration. Physiol Behav 1982;28:749-754.
128. Wright DE, Seroogy KB, Lundgren KH, Davis BM, Jennes L. Comparative localization of serotonin 1A, 1C, and 2 receptor subtype mRNAs in rat brain. J Comp Neurol 1995;351:357-373.
129. Yen CA, Stanger RL, Millman N. Ataractic suppression of isolated-induced aggressive behaviour. Arch Int Pharmacodyn 1959;123:179-185.
130. Yocca FD, Wright RN, Margraf RR, Eison AS. 8-OH-DPAT and buspirone analogs inhibit the ketanserin-sensitive quipazine-induced head shake response in rats. Pharmacol Biochem Behav 1990;35:251-254.