Skip to main content
SpringerLink
Log in

Serotonin Receptor Subtypes

Their Evolution and Clinical Relevance

  • Published:
CNS Drugs Aims and scope Submit manuscript

Summary

The multiplicity of serotonin (5-hydroxytryptamine; 5-HT) receptors far exceeds previous predictions. This overview attempts to answer the frequently asked question ‘Why are there so many serotonin receptor subtypes?’ The data indicate that although there has been a recent flurry of reports in the literature regarding the identification of ‘new’ serotonin receptor subtypes, the ‘primordial’ serotonin receptor evolved over 750 million years ago, a date likely to predate the evolution of muscarinic, dopaminergic and adrenergic receptor systems. This analysis also predicts that a significant number of both mammalian and invertebrate G protein-coupled serotonin receptor subtypes remain to be identified. The clinical significance of this multiplicity is only beginning to be appreciated. However, it is already evident that modulation of serotonin receptors can have important therapeutic benefits and the clinical usage of selective serotonin receptor subtype agents is very likely to increase significantly in the years ahead.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Peroutka SJ. The molecular biology of 5-hydroxytryptamine receptor subtypes. Synapse. In press

  2. Peroutka SJ, Howell TA. The molecular evolution of G protein-coupled receptors: focus on 5-hydroxytryptamine receptors. Neuropharmacology 1994; 33: 319–24

    Article  PubMed  CAS  Google Scholar 

  3. Feng DF, Doolittle RF. Progressive alignment and phylogenetic tree construction of protein sequences. Meth Enzymol 1990; 183: 375–87

    Article  PubMed  CAS  Google Scholar 

  4. Peroutka SJ. In: Peroutka SJ, editor. Handbook of receptors and channels: G protein-coupled receptors. Vol. 1. Boca Raton: CRC Press, 1994: 335

    Google Scholar 

  5. Wilson EO, Eisner T, Briggs WR, et al. Life on earth. Stamford: Sinauer Associates, 1973; 1033

    Google Scholar 

  6. Guan X. Miscellaneous receptors. In: Peroutka SJ, editor. Handbook of receptors and channels: G protein-coupled receptors. Vol. 1. Boca Raton: CRC Press, 1994: 299–328

    Google Scholar 

  7. Venter JC, DiPorzio U, Robinson DA, et al. Evolution of neurotransmitter receptor systems. Prog Neurobiol 1988; 30: 105–69

    Article  PubMed  CAS  Google Scholar 

  8. Goa KL, Ward A. Buspirone: a preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. Drugs 1986; 32: 114–29

    Article  PubMed  CAS  Google Scholar 

  9. Lucki I. Behavioral studies of serotonin receptor agonists as antidepressant drugs. J Clin Psychiatry 1991; 52Suppl. 12: 24–31

    PubMed  Google Scholar 

  10. Wieland S, Lucki I. Antidepressant-like activity of 5-HT1A agonists measured with the forced swim test. Psychopharmacology 1990; 101: 497–504

    Article  PubMed  CAS  Google Scholar 

  11. Dechant KL, Clissold SP. Sumatriptan: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the acute treatment of migraine and cluster headache. Drugs 1992; 43: 776–98

    Article  PubMed  CAS  Google Scholar 

  12. Goadsby PJ. Diagnosis and optimum treatment of migraine. CNS Drugs 1994; 1: 245–53

    Article  Google Scholar 

  13. Deliganis AV, Peroutka SJ. 5-Hydroxytryptamine1D receptor agonism predicts antimigraine effect. Headache 1991; 31: 228–31

    Article  PubMed  CAS  Google Scholar 

  14. Peroutka SJ, McCarthy BG. Sumatriptan (GR 43175) interacts selectively with 5-HT1B and 5-HT1D binding sites. Eur J Pharmacol 1989; 163: 133–6

    Article  PubMed  CAS  Google Scholar 

  15. Saxena PR, Ferrari MD. 5-HT1-like receptor agonists and the pathophysiology of migraine. Trends Pharmacol Sci 1989; 10: 200–4

    Article  PubMed  CAS  Google Scholar 

  16. Goodman WK, McDougle CJ, Price LH. Pharmacotherapy of obsessive-compulsive disorder. J Clin Psychiatry 1992; 53(Suppl.): 29–37

    PubMed  Google Scholar 

  17. Joffe RT, Schuler DR. An open study of buspirone augmentation of serotonin reuptake inhibitors in refractory depression. J Clin Psychiatry 1993; 54: 269–71

    PubMed  CAS  Google Scholar 

  18. Stanislav SW, Fabre T, Crismon ML, et al. Buspirone’s efficacy in organic-induced aggression. J Clin Psychiatry 1994; 14: 126–30

    CAS  Google Scholar 

  19. Goadsby PJ. Migraine: diagnosis and optimum treatment. Curr Therapeut 1994; 35: 53–61

    Google Scholar 

  20. Peroutka SJ, Snyder SH. Long-term antidepressant treatment decreases spiroperidol-labelled serotonin receptor binding. Science 1980; 210: 88–90

    Article  PubMed  CAS  Google Scholar 

  21. Fitton A, Heel RC. Clozapine: a review of its pharmacological properties and therapeutic use in schizophrenia. Drugs 1990; 40: 722–47

    Article  PubMed  CAS  Google Scholar 

  22. Grant S, Fitton A. Risperidone: a review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs 1994; 48: 253–73

    Article  PubMed  CAS  Google Scholar 

  23. Borison RL, Diamond BI, Pathiraja A, et al. Risperidone - clinical efficacy and safety in schizophrenia. Psychopharmacol Bull 1992; 28: 213–8

    PubMed  CAS  Google Scholar 

  24. Casey DE. Clozapine - neuroleptic-induced EPS and tardive dyskinesia. Psychopharmacology 1989; 99: S47–S53

    Article  PubMed  Google Scholar 

  25. Dassa D, Kaladjian A, Azorin JM, et al. Clozapine in the treatment of psychotic refractory depression. Br J Psychiatry 1993; 163: 822–4

    Article  PubMed  CAS  Google Scholar 

  26. Frankenburg FR, Zanarini MC. Use of clozapine in non-schizophrenic patients. Harvard Rev Psychiatry 1994; 2: 142–50

    Article  CAS  Google Scholar 

  27. Banov MD, Zarate CA, Tohen M, et al. Clozapine therapy in refractory affective disorders: polarity predicts response in long-term follow-up. J Clin Psychiatry 1994; 55: 295–300

    PubMed  CAS  Google Scholar 

  28. Pfeiffer C, Wagner ML. Clozapine therapy for Parkinson’s disease and other movement disorders. Am J Hosp Pharm 1994; 51: 3047–53

    PubMed  CAS  Google Scholar 

  29. Handley SL, Dursun SM. Serotonin and Tourette’s syndrome: movements such as head-shakes and wet-dog-shakes may mimic human tics. Adv Biosci 1992; 85: 235–53

    CAS  Google Scholar 

  30. Brogden RN, Sorkin EM. Ketanserin: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in hypertension and peripheral vascular disease. Drugs 1990; 40: 903–49

    Article  PubMed  CAS  Google Scholar 

  31. Markham A, Sorkin EM. Ondansetron: an update of its therapeutic use in chemotherapy-induced and postoperative nausea and vomiting. Drugs 1993; 45: 931–52

    Article  PubMed  CAS  Google Scholar 

  32. Lee CR, Plosker GL, McTavish D. Tropisetron: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential as an antiemetic. Drugs 1993; 46: 925–43

    Article  PubMed  CAS  Google Scholar 

  33. Plosker GL, Goa KL. Granisetron: a review of its pharmacological properties and therapeutic use as an antiemetic. Drugs 1991; 42: 805–24

    Article  PubMed  CAS  Google Scholar 

  34. Diehl V, Marty M. Efficacy and safety of antiemetics. Cancer Treat Reports 1994; 20: 379–92

    Article  CAS  Google Scholar 

  35. Rudorfer MV, Manji HK, Potter WZ. Comparative tolerability profiles of the newer versus older antidepressants. Drug Saf 1994; 10: 18–46

    Article  PubMed  CAS  Google Scholar 

  36. Martin P, Gozlan H, Puech AJ. 5-HT3 receptor antagonists reduce helpless behaviour in rats. Eur J Pharmacol 1992; 212: 73–8

    Article  PubMed  CAS  Google Scholar 

  37. Stefanski R, Palejko W, Bidzinski A, et al. Serotonergic innervation of the hippocampus and nucleus accumbens septi and the anxiolytic-like action of the 5-HT3 receptor antagonists. Neuropharmacology 1993; 32: 987–93

    Article  PubMed  CAS  Google Scholar 

  38. Costall B, Naylor RJ. Anxiolytic potential of 5-HT3 receptor antagonists. Pharmacol Toxicol 1992; 70: 157–62

    Article  PubMed  CAS  Google Scholar 

  39. Eglen RM. Recent developments in 5-HT4 receptor research. Curr Opin Invest Drugs 1993; 2: 645–9

    Google Scholar 

  40. Meltzer HY, Lowy MT. The serotonin hypothesis of depression. In: Meltzer, et al., editors. Psychopharmacology. The third generation of progress. New York: Raven Press, 1987: 513–26

    Google Scholar 

  41. Blackwell B. Adverse effects of antidepressant drugs. Part I: Monoamine oxidase inhibitors and tricyclics. Drugs 1981; 21: 201–19

    Article  PubMed  CAS  Google Scholar 

  42. Boyer WF, Feighner JP. Side effects of the selective serotonin reuptake inhibitors. In: Feighner & Boyer, editors. Selective serotonin reuptake inhibitors: the clinical use of citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. Perspectives in Psychiatry, Vol. 1. Chichester: John Wiley and Sons, 1991: 133–52

    Google Scholar 

  43. Rosenberg R. Drug treatment of panic disorder. Pharmacol Toxicol 1993; 72: 344–53

    Article  PubMed  CAS  Google Scholar 

  44. Handley S. Future prospects for the pharmacological treatment of anxiety. CNS Drugs 1994; 2: 397–414

    Article  Google Scholar 

  45. Humble M, Wistedt B. Serotonin, panic disorder and agoraphobia: short term and long term efficacy of citalopram in panic disorders. Int Clin Psychopharmacol 1992; 6Suppl. 5: 21–39

    Article  PubMed  Google Scholar 

  46. Zohar J, Zohar-Kadouch RC, Kindler S. Current concepts in the pharmacological treatment of obsessive-compulsive disorder. Drugs 1992; 43: 210–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Palo Alto Institute for Molecular Medicine, 1025 Tournament Drive, Hillsborough, California, 94010, USA

    Stephen J. Peroutka

Authors
  1. Stephen J. Peroutka
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peroutka, S.J. Serotonin Receptor Subtypes. CNS Drugs 4 (Suppl 1), 18–28 (1995). https://doi.org/10.2165/00023210-199500041-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199500041-00005

Keywords

Search

Navigation