Cellular and Molecular Neurobiology

, Volume 28, Issue 4, pp 491–499

Recent Development in Studies of Tetrahydroprotoberberines: Mechanism in Antinociception and Drug Addiction

  • Hongyuan Chu
  • Guozhang Jin
  • Eitan Friedman
  • Xuechu Zhen
Original Paper

Abstract

The tetrahydroprotoberberines (THPBs) are compounds isolated from Chinese herbs that possess a unique pharmacological profile as D2 dopamine receptor antagonists and D1 receptor agonists. l-Tetrahydropalmatine (l-THP) and l-stepholidine (SPD), members of the THPB family, were shown to have potential clinical use in the treatment of pain. However, their mechanism of action is not clear. In the past decades, Chinese scientists have made a great deal of effort to explore the mechanisms by which the THPBs and its analogues elicit antinociception and their potential utility in treating drug abuse. It is now clear that the antinociception produced by l-THP is related to inhibition of D2 dopamine receptors. The present review focuses on the recent progress made in understanding the mechanisms of l-THP- and l-SPD-mediated antinociception and the sequel of drug addiction.

Keywords

Tetrahydroprotoberberines l-Tetrahydropalmatine l-Stepholidine Dopamine receptor Antinociception Drug addiction 

Abbreviations

str

Striatum

ac

Nucleus accumbens

sc

Somatosensory cortex

th

Thalamus

PAG

Periaqueductal gray

dh

Dorsal horn

References

  1. Adinoff B (2004) Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry 12:305–320CrossRefPubMedGoogle Scholar
  2. Berger SP, Hall S, Mickalian JD, Reid MS, Crawford CA, Delucchi K, Carr K, Hall S (1996) Haloperidol antagonism of cue-elicited cocaine craving. Lancet 347:504–508CrossRefPubMedGoogle Scholar
  3. Bittencourt AL, Takahashi RN (1997) Mazindol and lidocaine are antinociceptives in the mouse formalin model: involvement of dopamine receptor. Eur J Pharmacol 330:109–113CrossRefPubMedGoogle Scholar
  4. Chen LF, Gao JZ, Wang FC (1986) Analgesic and antipyretic effects of l-stepholidine without addiction. Zhongguo Yao Li Xue Bao 7:311–314PubMedGoogle Scholar
  5. Coffin VL, Latranyi MB, Chipkin RE (1989) Acute extrapyramidal syndrome in Cebus monkeys: development mediated by dopamine D2 but not D1 receptors. J Pharmacol Exp Ther 249:769–774PubMedGoogle Scholar
  6. Frussa-Filho R, Rocha JB, Conceicao IM, Mello CF, Pereira ME (1996) Effects of dopaminergic agents on visceral pain measured by the mouse writhing test. Arch Int Pharmacodyn Ther 331:74–93PubMedGoogle Scholar
  7. Gilbert A-K, Franklin KBJ (2001) Characterization of the analgesic properties of nomifensine in rats. Pharmacol Biochem Behav 68:783–787CrossRefPubMedGoogle Scholar
  8. Grech DM, Spealman RD, Bergman J (1996) Self-administration of D1 receptor agonists by squirrel monkeys. Psychopharmacology 125:97–104CrossRefPubMedGoogle Scholar
  9. Guo X, Wang LM, Liu J, Jin GZ (1997) Characteristics of tetrahydroprotoberberines on dopamine D1 and D2 receptors in calf striatum. Zhongguo Yao Li Xue Bao 18:225–230PubMedGoogle Scholar
  10. Haney M, Collins ED, Ward AS, Foltin RW, Fischman MW (1999) Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans. Psychopharmacology 143:102–110CrossRefPubMedGoogle Scholar
  11. Herz A, Millan MJ (1990) Opioids and opioid receptors mediating antinociception at various levels of the neuraxis. Physiol Bohemoslov 39:395–401PubMedGoogle Scholar
  12. Hu JY, Jin GZ (1999a) Effect of tetrahydropalmatine analogs on Fos expression induced by formalin-pain. Zhongguo Yao Li Xue Bao 20:193–200PubMedGoogle Scholar
  13. Hu JY, Jin GZ (1999b) Supraspinal D2 receptor involved in antinociception induced by l-tetrahydropalmatine. Zhongguo Yao Li Xue Bao 20:715–719PubMedGoogle Scholar
  14. Hu JY, Jin GZ (2000) Arcuate nucleus of hypothalamus involved in analgesic action of l-THP. Acta Pharmacol Sin 21:439–444PubMedGoogle Scholar
  15. Huang KX, Jin GZ (1992) The antagonistic effects of tetrahydroprotoberberines on dopamine receptors: electrophysiological studies. Sci China B 35:688–696PubMedGoogle Scholar
  16. Huang KX, Sun BC, Jin GZ (1992) (−)-Stepholidine: a dopamine receptor antagonist shows agonistic effect on rotational behavior in 6-hydroxydopamine-lesioned rats. Zhongguo Yao Li Xue Bao 13:17–22PubMedGoogle Scholar
  17. Jin GZ (1987) (−)-Tetrahydropalmatine and its analogues as new dopamine receptor antagonists. Trends Pharmacol Sci 8:81–82CrossRefGoogle Scholar
  18. Jin GZ (2001) Discoveries in the voyage of Corydalis research. Shanghai Scientific & Technical Publishers, ShanghaiGoogle Scholar
  19. Jin GZ, Huang KX, Sun BC (1992) Dual actions of (−)-stepholidine on dopamine receptor subtypes after substantia nigra lesion. Neurochem Int 20(Suppl):175S–178SCrossRefPubMedGoogle Scholar
  20. Jin GZ, Sun BC (1995) Neuropharmacological effects of (−)-stepholidine and its analogues on brain dopaminergic system. Adv Exp Med Biol 363:27–28PubMedGoogle Scholar
  21. Jin GZ, Zhu ZT, Fu Y (2002) (−)-Stepholidine: a potential novel antipsychotic drug with dual D1 receptor agonist and D2 receptor antagonist actions. Trends Pharmacol Sci 23:4–7CrossRefPubMedGoogle Scholar
  22. Kin KC, Zhen XF, Hsu B (1964) Studies on the pharmacological action of Corydalis XII: the effects of isomers of tetrahydropalmatine(THP) on central nervous system. Acta Physiol Sin 27:47–57Google Scholar
  23. Leshner AI (1997) Addiction is a brain disease, and it matters. Science 278:45–47CrossRefPubMedGoogle Scholar
  24. Liu ZH, Jin WQ, Zhang HP, Chen XJ, Jin GZ (2003) Suppression of morphine-induced conditioned place preference by l-12-chloroscoulerine, a novel dopamine receptor ligand. Pharmacol Biochem Behav 75:289–294CrossRefPubMedGoogle Scholar
  25. Magnusson JE, Fisher K (2000) The involvement of dopamine in nociception: the role of D1 and D2 receptors in the dorsolateral striatum. Brain Res 855:260–266CrossRefPubMedGoogle Scholar
  26. Malhotra J, Chaudhary G, Gupta YK (2000) Dopaminergic involvement in adenosine A1 receptor-mediated antinociception in the tail flick latency model in mice. Methods Find Exp Clin Pharmacol 22:37–41CrossRefPubMedGoogle Scholar
  27. Mantsch JR, Li SJ, Risinger R, Awad S, Katz E, Baker DA, Yang Z (2007) Levo-tetrahydropalmatine attenuates cocaine self-administration and cocaine-induced reinstatement in rats. Psychopharmacol (Berl) 192:581–591CrossRefGoogle Scholar
  28. McBride WJ, Murphy JM, Ikemoto S (1999) Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. Behav Brain Res 101:129–152CrossRefPubMedGoogle Scholar
  29. Michael BG, Negus SS, Nancy KM (1998) Antinociceptive effects of monoamine reuptake inhibitors administered alone or in combination with mu opioid agonists in rhesus monkeys. Psychopharmacology 135:99–106CrossRefGoogle Scholar
  30. Pelissier T, Laurido C, Hernandez A, Constandil L, Eschalier A (2006) Biphasic effect of apomorphine on rat nociception and effect of dopamine D2 receptor antagonists. Eur J Pharmacol 546:40–47CrossRefPubMedGoogle Scholar
  31. Pierce RC, Kumaresan V (2006) The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 30:215–238CrossRefPubMedGoogle Scholar
  32. Platt DM, Rowlett JK, Spealman RD (2000) Dissociation of cocaine-antagonist properties and motoric effects of the D1 receptor partial agonists SKF 83959 and SKF 77434. J Pharmacol Exp Ther 293:1017–1026PubMedGoogle Scholar
  33. Pulvirenti L, Koob GF (1994) Dopamine receptor agonists, partial agonists and psychostimulant addiction. Trends Pharmacol Sci 15:374–379CrossRefPubMedGoogle Scholar
  34. Roane DS, Bounds JK, Ang C-Y, Adloo AA (1998) Quinpirole-induced alterations of tail temperature appear as hyperalgesia in the radiant heat tail-flick test. Pharmacol Biochem Behav 59:77–82CrossRefPubMedGoogle Scholar
  35. Shimizu T, Iwata S-i, Morioka H, Masuyama T, Fukuda T, Nomoto M (2004) Antinociceptive mechanism of -DOPA. Pain 110:246–249CrossRefPubMedGoogle Scholar
  36. Spealman RD, Jack B, Rosenzweig-Lipson S (1997) Differential modulation of behavioral effects of cocaine by low- and high-efficacy D1 agonists. Psychopharmacology 133:283–292CrossRefPubMedGoogle Scholar
  37. Taylor BK, Joshi C, Uppal H (2003) Stimulation of dopamine D2 receptors in the nucleus accumbens inhibits inflammatory pain. Brain Res 987:135–143CrossRefPubMedGoogle Scholar
  38. Wang W, Zhou Y, Sun J, Pan L, Kang L, Dai Z, Yu R, Jin G, Ma L (2007) The effect of l-stepholidine, a novel extract of Chinese herb, on the acquisition, expression, maintenance, and re-acquisition of morphine conditioned place preference in rats. Neuropharmacology 52:355–361CrossRefPubMedGoogle Scholar
  39. Warner EA, Kosten TR, O’Connor PG (1997) Pharmacotherapy for opioid and cocaine abuse. Medical Clin North Am 81:909–925CrossRefGoogle Scholar
  40. Weed MR, Paul IA, Dwoskin LP, Moore SE, Woolverton WL (1997) The relationship between reinforcing effects and in vitro effects of D1 agonists in monkeys. J Pharmacol Exper Ther 283:29–38Google Scholar
  41. Wise RA (1998) Drug-activation of brain reward pathways. Drug Alcohol Depend 51:13–22CrossRefPubMedGoogle Scholar
  42. Wise RA (2002) Brain reward circuitry: insights from unsensed incentives. Neuron 36:229–240CrossRefPubMedGoogle Scholar
  43. Xu J, Zheng LZ, Jin GZ (1982) Relevance of brain prostaglandins to central effects of l-tetrahydropalmatine. Zhongguo Yao Li Xue Bao 3:217–220PubMedGoogle Scholar
  44. Xu SX, Yu LP, Han YR, Chen Y, Jin GZ (1989) Effects of tetrahydroprotoberberines on dopamine receptor subtypes in brain. Zhongguo Yao Li Xue Bao 10:104–110PubMedGoogle Scholar
  45. Yang Z, Chen H, Hao W, Jin G, Li S (2006) Medication of L-tetrahydropalmatine increased the abstinence rate in heroin addicts. College on Problems of Drug Dependence 2006 Meeting Abstracts, Scottsdale, AZ, Available at http://biopsych.com:81/CPDD06_Web/MeetProgAbSearch_06.html
  46. Yoshimura M, North RA (1983) Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature 305:529–530CrossRefPubMedGoogle Scholar
  47. Zarrindast M-R, Nassiri-Rad S, Pazouki M (1999) Effects of dopaminergic agents on antinociception in formalin test. Gen Pharmacol 32:517–522CrossRefPubMedGoogle Scholar
  48. Zhang ZD, Jin GZ, Xu SX, Yu LP, Chen Y, Jiang FY, Zhang YR, Sun Z, Ding YL, Bian CF et al (1986) Effects of l-stepholidine on the central nervous and cardiovascular systems. Zhongguo Yao Li Xue Bao 7:522–526PubMedGoogle Scholar
  49. Zou LL, Liu J, Jin GZ (1997) Involvement of receptor reserve in D1 agonistic action of (-)-stepholidine in lesioned rats. Biochem Pharmacol 54:233–240CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Hongyuan Chu
    • 1
  • Guozhang Jin
    • 1
  • Eitan Friedman
    • 2
  • Xuechu Zhen
    • 1
  1. 1.State Key laboratory of Drug Research, Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina
  2. 2.Department of Physiology & PharmacologyCity University of New York Medical SchoolNew YorkUSA

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