Skip to main content
SpringerLink
Log in

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

  • Original Paper
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

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.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

str:

Striatum

ac:

Nucleus accumbens

sc:

Somatosensory cortex

th:

Thalamus

PAG:

Periaqueductal gray

dh:

Dorsal horn

References

  • Adinoff B (2004) Neurobiologic processes in drug reward and addiction. Harv Rev Psychiatry 12:305–320

    Article  PubMed  Google Scholar 

  • 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 347:504–508

    Article  CAS  PubMed  Google Scholar 

  • Bittencourt AL, Takahashi RN (1997) Mazindol and lidocaine are antinociceptives in the mouse formalin model: involvement of dopamine receptor. Eur J Pharmacol 330:109–113

    Article  CAS  PubMed  Google Scholar 

  • Chen LF, Gao JZ, Wang FC (1986) Analgesic and antipyretic effects of l-stepholidine without addiction. Zhongguo Yao Li Xue Bao 7:311–314

    CAS  PubMed  Google Scholar 

  • 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 249:769–774

    CAS  PubMed  Google Scholar 

  • 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 331:74–93

    CAS  PubMed  Google Scholar 

  • Gilbert A-K, Franklin KBJ (2001) Characterization of the analgesic properties of nomifensine in rats. Pharmacol Biochem Behav 68:783–787

    Article  CAS  PubMed  Google Scholar 

  • Grech DM, Spealman RD, Bergman J (1996) Self-administration of D1 receptor agonists by squirrel monkeys. Psychopharmacology 125:97–104

    Article  CAS  PubMed  Google Scholar 

  • 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 18:225–230

    PubMed  Google Scholar 

  • 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 143:102–110

    Article  CAS  PubMed  Google Scholar 

  • Herz A, Millan MJ (1990) Opioids and opioid receptors mediating antinociception at various levels of the neuraxis. Physiol Bohemoslov 39:395–401

    CAS  PubMed  Google Scholar 

  • Hu JY, Jin GZ (1999a) Effect of tetrahydropalmatine analogs on Fos expression induced by formalin-pain. Zhongguo Yao Li Xue Bao 20:193–200

    CAS  PubMed  Google Scholar 

  • Hu JY, Jin GZ (1999b) Supraspinal D2 receptor involved in antinociception induced by l-tetrahydropalmatine. Zhongguo Yao Li Xue Bao 20:715–719

    CAS  PubMed  Google Scholar 

  • Hu JY, Jin GZ (2000) Arcuate nucleus of hypothalamus involved in analgesic action of l-THP. Acta Pharmacol Sin 21:439–444

    CAS  PubMed  Google Scholar 

  • Huang KX, Jin GZ (1992) The antagonistic effects of tetrahydroprotoberberines on dopamine receptors: electrophysiological studies. Sci China B 35:688–696

    CAS  PubMed  Google Scholar 

  • 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 13:17–22

    CAS  PubMed  Google Scholar 

  • Jin GZ (1987) (−)-Tetrahydropalmatine and its analogues as new dopamine receptor antagonists. Trends Pharmacol Sci 8:81–82

    Article  CAS  Google Scholar 

  • Jin GZ (2001) Discoveries in the voyage of Corydalis research. Shanghai Scientific & Technical Publishers, Shanghai

    Google Scholar 

  • Jin GZ, Huang KX, Sun BC (1992) Dual actions of (−)-stepholidine on dopamine receptor subtypes after substantia nigra lesion. Neurochem Int 20(Suppl):175S–178S

    Article  CAS  PubMed  Google Scholar 

  • Jin GZ, Sun BC (1995) Neuropharmacological effects of (−)-stepholidine and its analogues on brain dopaminergic system. Adv Exp Med Biol 363:27–28

    CAS  PubMed  Google Scholar 

  • 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 23:4–7

    Article  CAS  PubMed  Google Scholar 

  • 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 27:47–57

    CAS  Google Scholar 

  • Leshner AI (1997) Addiction is a brain disease, and it matters. Science 278:45–47

    Article  CAS  PubMed  Google Scholar 

  • 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 75:289–294

    Article  CAS  PubMed  Google Scholar 

  • Magnusson JE, Fisher K (2000) The involvement of dopamine in nociception: the role of D1 and D2 receptors in the dorsolateral striatum. Brain Res 855:260–266

    Article  CAS  PubMed  Google Scholar 

  • 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 22:37–41

    Article  CAS  PubMed  Google Scholar 

  • 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) 192:581–591

    Article  CAS  Google Scholar 

  • McBride WJ, Murphy JM, Ikemoto S (1999) Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. Behav Brain Res 101:129–152

    Article  CAS  PubMed  Google Scholar 

  • 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 135:99–106

    Article  Google Scholar 

  • 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 546:40–47

    Article  CAS  PubMed  Google Scholar 

  • Pierce RC, Kumaresan V (2006) The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 30:215–238

    Article  CAS  PubMed  Google Scholar 

  • 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 293:1017–1026

    CAS  PubMed  Google Scholar 

  • Pulvirenti L, Koob GF (1994) Dopamine receptor agonists, partial agonists and psychostimulant addiction. Trends Pharmacol Sci 15:374–379

    Article  CAS  PubMed  Google Scholar 

  • 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 59:77–82

    Article  CAS  PubMed  Google Scholar 

  • Shimizu T, Iwata S-i, Morioka H, Masuyama T, Fukuda T, Nomoto M (2004) Antinociceptive mechanism of -DOPA. Pain 110:246–249

    Article  CAS  PubMed  Google Scholar 

  • Spealman RD, Jack B, Rosenzweig-Lipson S (1997) Differential modulation of behavioral effects of cocaine by low- and high-efficacy D1 agonists. Psychopharmacology 133:283–292

    Article  CAS  PubMed  Google Scholar 

  • Taylor BK, Joshi C, Uppal H (2003) Stimulation of dopamine D2 receptors in the nucleus accumbens inhibits inflammatory pain. Brain Res 987:135–143

    Article  CAS  PubMed  Google Scholar 

  • 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 52:355–361

    Article  CAS  PubMed  Google Scholar 

  • Warner EA, Kosten TR, O’Connor PG (1997) Pharmacotherapy for opioid and cocaine abuse. Medical Clin North Am 81:909–925

    Article  CAS  Google Scholar 

  • 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 283:29–38

    CAS  Google Scholar 

  • Wise RA (1998) Drug-activation of brain reward pathways. Drug Alcohol Depend 51:13–22

    Article  CAS  PubMed  Google Scholar 

  • Wise RA (2002) Brain reward circuitry: insights from unsensed incentives. Neuron 36:229–240

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Zheng LZ, Jin GZ (1982) Relevance of brain prostaglandins to central effects of l-tetrahydropalmatine. Zhongguo Yao Li Xue Bao 3:217–220

    CAS  PubMed  Google Scholar 

  • 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 10:104–110

    CAS  PubMed  Google Scholar 

  • 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

  • Yoshimura M, North RA (1983) Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature 305:529–530

    Article  CAS  PubMed  Google Scholar 

  • Zarrindast M-R, Nassiri-Rad S, Pazouki M (1999) Effects of dopaminergic agents on antinociception in formalin test. Gen Pharmacol 32:517–522

    Article  CAS  PubMed  Google Scholar 

  • 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 7:522–526

    CAS  PubMed  Google Scholar 

  • Zou LL, Liu J, Jin GZ (1997) Involvement of receptor reserve in D1 agonistic action of (-)-stepholidine in lesioned rats. Biochem Pharmacol 54:233–240

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the 973-plan of Ministry of science and Technology (973-2003CB5154000).

Author information

Authors and Affiliations

  1. State Key laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Rm# 2-315, Shanghai, 201203, China

    Hongyuan Chu, Guozhang Jin & Xuechu Zhen

  2. Department of Physiology & Pharmacology, City University of New York Medical School, New York, USA

    Eitan Friedman

Authors
  1. Hongyuan Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guozhang Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eitan Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuechu Zhen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuechu Zhen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chu, H., Jin, G., Friedman, E. et al. Recent Development in Studies of Tetrahydroprotoberberines: Mechanism in Antinociception and Drug Addiction. Cell Mol Neurobiol 28, 491–499 (2008). https://doi.org/10.1007/s10571-007-9179-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-007-9179-4

Keywords

Search

Navigation