Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Neuroleptic properties of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) with selective antidopaminergic activity

  • 23 Accesses

  • 70 Citations


A new benzamide, cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) exhibited more potent and longer-lasting inhibitory effects on apomorphine-induced behaviours (stereotyped behaviour, emesis and hypothermia), and methamphetamine-induced stereotyped behaviour, conditioned avoidance response and open field behaviour than either structurally similar benzamides (YM-0850 and sulpiride) or calssical neuroleptics [chlorpromazine(CPZ) and haloperidol(HPD)]. Such inhibitory effects of YM-09151-2 relative to cataleptogenicity were greater than those of CPZ and HPD. In contrast, sulpiride elicited few of the neuroleptic effects described above. YM-09151-2, a potent inhibitor for dopamine-sensitive adenylate cyclase (Ki: 3.0 nM) reduced, in a selective manner, the binding of [3H]dopamine to the dopamine D1 receptor (Ki: 4.8 nM) associated with adenylate cyclase rather than to the dopamine D2 receptor (Ki: 0.98 μM) independent of adenylate cyclase. Sulpiride, on the contrary, inhibited only the binding to the dopamine D2 receptor. CPZ and HPD antagonized [3H]dopamine non-selectively at the two distinct dopaminergic receptors. These results suggest that YM-09151-2 is a potent and long-lasting neuroleptic with a highly selective blocking action on the dopamine D1 receptor.

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


  1. Borenstein P, Cujo Ph, Champion C, Olevestein C (1968) Etude l'un nouveau psychotrope, le sulpiride (1403 RD). Ann Med Psychol 2:90–107

  2. Brown BL, Ekins RP, Albano JDM (1972) Saturation assay for cyclic AMP using endogenous binding protein. Advan. Cyclic Nucleotide Res 2:25–50

  3. Constein J, Protain P, Schwartz JC (1975) Rapid and dissociation changes in sensitivies of different dopamine receptors in mouse brain. Nature 257:405–407

  4. Cools A, Van Rossum JW (1976) Excitation-mediating and inhibition-mediating dopamine-receptors: A new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data. Psychopharmacologia 45:243–254

  5. Costall B, Funderburk WH, Leonard CA, Naylor RJ (1978) Assessment of the neuroleptic potential of some novel benzamide, butyrophenone, phenothiazine and indole derivatives. J Pharm Pharmac 30:771–778

  6. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483

  7. Di Chiara G, Porceddu ML, Vargiu L, Argiolas A, Gessa GL (1976) Evidence for dopamine receptors mediating sedation in the mouse brain. Nature 264:564–567

  8. Di Chiara G, Corsini GU, Mereu GP, Tissari A, Gessa GL (1978) Self-inhibitory dopamine receptors: Their role in the biochemical and behavioral effects of low doses of apomorphine. In: Roberts PJ, Woodroff GN, Iversen LL (eds) Advances in biochemical psychopharmacology, Vol 19. Raven Press, New York, pp 275–291

  9. Elliot PNC, Jenner P, Huzing G, Marsden CD, Miller R (1977) Substituted benzamide as cerebral dopamine antagonists in rodents. Neuropharmacology 16:333–342

  10. Hall CS (1934) Emotional behavior in the rat, I: Defacation and urination as measures of individual differences emotionality. J Comp Psychol 18:385–403

  11. Iwanami S, Takashima M, Hirata Y, Usuda S (1980) The 100th Annual Meeting of the Pharmaceutical Society of Japan, April 2, Tokyo, Japan

  12. Janssen PAJ, Niemegeers CJE, Schellekens KHL (1965) Is it possible to predict the clinical effects of neuroleptic drugs (major tranquilizer) from animal data? Part I. Neuroleptic activity spectra for rats. Arzneim Forsch 15:104–117

  13. Jenner P, Clow A, Reavill C, Theodoru A, Marsden CD (1978) A behavioral and biochemical comparison of dopamine receptor blockade produced by haloperidol with that produced by substituted benzamide drugs. Life Sci 23:545–550

  14. Kebabian JW, Calne DB (1969) Multiple receptors are dopamine. Nature 277:93–96

  15. Laville CL, Margarit J (1979) Sur les neurologiques centraux de sulpiride. Pathol Biol 17:71–75

  16. Litchfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–113

  17. Nishikori K, Noshiro O, Sano K, Maeno H (1980) Characterization, solubilization and separation of two distinct dopamine receptors in canine caudate nucleus. J Biol Chem 255:10909–10915

  18. Puech AJ, Simon P, Boissier JR (1978) Benzamides and classical neuroleptics; Comparison of their actions using 6 apomorphine-induced effects. Eur J Pharmacol 50:291–300

  19. Riffee WH, Wilcox RE, Smith RV (1979) Stereotypic and hypothermic effects of apomorphine and N-n-propylnorapomorphine in mice. Eur J Pharmacol 54:273–277

  20. Rotrosen J, Wallach MB, Angrist B, Gershon S (1972) Antagonism of apomorphine-induced stereotypy and emesis in dogs by thioridazine, haloperidol and pimozide. Psychopharmacologia 26:185–194

  21. Sano K, Nishikori K, Noshiro O, Maeno H (1979a) Reconstitution of dopamine-sensitive adenylate cyclase from dissociated components in canine caudate nucleus. Archs Biochem Biophys 197:285–293

  22. Sano K, Noshiro O, Katsuda K, Nishikori K, Maeno H (1979b) Dopamine receptors and dopamine-sensitive adenylate cyclase in canine caudate nucleus. Biochem Pharmacol 28:3617–3626

  23. Seeman P, Chau-Wong M, Tedesco J, Wong K (1975) Brain receptors for antipsychotic drugs and dopamine: Direct binding assays. Proc Nat Acad Sci USA 72:4376–4380

  24. Spano PF, Govoni S, Trabuchi M (1978) Studies on the pharmacological properties of dopamine receptors in various areas of the central nervous system. In: Roberts PJ, Woodruff GN, Iversen LL (eds) Advances in biochemical psychopharmacology, Vol 19. Raven Press, New York, pp 155–165

  25. Stanley M, Lautin A, Rotrosen J, Gershon S (1979) Antipsychotic efficacy of metoclopramide: Do DA/neuroleptic receptors mediate the action of antipsychotic drugs? ICRS Medical Science 7:322

  26. Toru M, Shimazono Y, Miyasaka M, Kokubo T, Mori Y, Nasu T (1972) A double-blind comparison of sulpiride with chlorpromazine in chronic schizophrenia. J Clin Pharmacol 12:221–229

  27. Usuda S, Sano K, Maeno H (1979) Pharmacological and biochemical studies on a new potential neuroleptic, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050). Arch Int Pharmacodyn 241:68–78

  28. Vinař OM, Kršiak M (1974) Prediction of neuroleptic effects from animal data. In: Forrest IS, Carr CJ, Usdin E (eds) The phenothiazines and structurally related drugs. Raven Press, New York, pp 675–683

  29. Weissman A (1968) Psychopharmacological effects of thiothixene and related compounds. Psychopharmacologia 12:142–157

Download references

Author information

Correspondence to Shinji Usuda.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Usuda, S., Nishikori, K., Noshiro, O. et al. Neuroleptic properties of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) with selective antidopaminergic activity. Psychopharmacology 73, 103–109 (1981). https://doi.org/10.1007/BF00429198

Download citation

Key words

  • 3-Pyrrolidinylbenzamide
  • YM-09151-2
  • Neuroleptic
  • Dopaminergic blockade
  • D1 and D2 receptors