EVALUATION OF THE INTERACTION OF PIPERINE WITH ANTIDEPRESSANT SERTRALINE AND ANALGESIC PENTAZOCINE, USING DIFFERENT ROUTES OF ADMINISTRATION IN ALBINO MICE

  • Shubham Atal M.G.M. Medical College, Indore
  • Pradeep Phadnis Bundelkhand medical college, Sagar
  • Savita Vyas M.G.M. Medical College, Indore
  • Gopal Gudsurkar M.G.M. Medical College. Indore
  • Ritesh Churihar M.G.M. Medical College, Indore

Abstract

ABSTRACT
Objective: To evaluate the effect of piperine on the antidepressant activity of sertraline and analgesic activity of pentazocine and to explore the effect
of using oral and parenteral routes of administration on the possible interactions.
Methods: Piperine was isolated from commercially obtained Piper nigrum extract. Swiss albino mice of either sex were divided into 8 groups (n=6)
receiving: 2% gum acacia (oral, intraperitoneally [i.p.]), standard drug (oral, i.p.), standard drug + piperine (oral, i.p.), piperine (oral, i.p.). Tail
suspension test (TST) was used for antidepressant effect and Eddy’s hot plate method for analgesic effect. Sertraline and pentazocine were used as
standard drugs (5 mg/kg) and piperine at 10 mg/kg.
Result: In the TST, piperine alone (both routes) decreased immobility time, but the effect was statistically insignificant. Both combination groups
(oral and i.p.) showed significantly better activity compared to sertraline oral and i.p. groups, respectively (p<0.05). Oral combination showed activity
comparable to i.p. combination (p>0.05). Piperine did not show any analgesic activity of its own (both routes). Piperine with pentazocine orally
showed significantly better activity compared to pentazocine (oral) at 1, 2, and 4 hrs, and analgesia at 0.5 hr which pentazocine oral did not. Parenteral
combination was significantly better than pentazocine (i.p.) group at 2 and 4 hrs and better than oral combination at 4 hrs.
Conclusion: Piperine has potential to be used in combination with pentazocine due to its bioenhancing effect and with sertraline due to a potentiating/
additive effect which can help reduce dose and adverse effects of these drugs.
Keywords: Piperine, Pentazocine, Sertraline, Albino mice, Bio enhancement, Potentiation.

Author Biographies

Shubham Atal, M.G.M. Medical College, Indore

Department of Pharmacology

Assistant Professor

Pradeep Phadnis, Bundelkhand medical college, Sagar

Department of Pharmacology

Associate Professor

Savita Vyas, M.G.M. Medical College, Indore

Department of Pharmacology

Associate Professor

Gopal Gudsurkar, M.G.M. Medical College. Indore

Department of Pharmacology

Postgraduate student

Ritesh Churihar, M.G.M. Medical College, Indore

Department of Pharmacology

Postgradute student

References

1. Atal CK. A breakthrough in drug bioavailability - A clue from age old
wisdom of Ayurveda. IDMA Bull 1979;10:483-4.
2. Sharma HL, SharmaKK. Pharmacodynamics. Principles of
Pharmacology. 2
ed. New Delhi: Paras Medical Publishers; 2011. p. 87.
3. Annamalai AR, Manavlan R. Trikatu - A bioavailability enhancer.
nd
Indian Drugs 1989;27:595-604.
4. Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug
bioavailability by piperine: Evidence that piperine is a potent inhibitor
of drug metabolism. J Pharmacol Exp Ther 1985;232(1):258-62.
5. Johri RK, Zutshi U. An Ayurvedic formulation ‘Trikatu’ and its
constituents. J Ethnopharmacol 1992;37(2):85-91.
6. Singh A, Duggal S. Piperine - Review of advances in pharmacology. Int
J Pharm Sci Nanotechnol 2009;2:615-20.
7. Atal CK, Zutshi U, Rao PG. Scientific evidence on the role of
Ayurvedic herbals on bioavailability of drugs. J Ethnopharmacol
1981;4(2):229-32.
8. Singh A, Deep A. Piperine: A bioenhancer. Int J Pharm Res Technol
2011;1:1-5.
9. Zutshi RK, Singh R, Zutshi U, Johri RK, Atal CK. Influence of piperine
on rifampicin blood levels in patients of pulmonary tuberculosis.
J Assoc Physicians India 1985;33(3):223-4.
10. Risorine Product Monograph. A New Paradigm in the Management
of T.B. Iamicon 2013. Available from: http://www.iamicon.in/wpcontent/uploads/2014/06/risorine-monograph.pdf.
[Last retrieved
on

2015
Oct
07].
11. Li S, Wang C, Li W, Koike K, Nikaido T, Wang MW. Antidepressant-
like effects of piperine and its derivative, antiepilepsirine. J Asian Nat
Prod Res 2007;9(3-5):421-30.
12. Sharma HL, Sharma KK. Antidepressants & Antimanic Drugs.
Principles of Pharmacology. 2
ed. New Delhi: Paras Medical
Publishers; 2011. p. 465-8.
nd
13. Pooja S, Agrawal R, Nyati P, Savitha V, Phadnis P. Analgesic activity of
Piper nigrum extract per se and its interaction with diclofenacsodium
and pentazocinein albino mice. Internet J Pharmacol 2007;5:3.
14. Hoskin PJ, Hanks GW. Opioid agonist-antagonist drugs in acute and
chronic pain states. Drugs 1991;41(3):326-44.
15. Kokate CK. Textbook of Practical Pharmacognosy. 4
ed. New Delhi:
Vallabh Prakashan; 2003. p. 143.
th
16. Lawless H. Oral chemical irritation: Psychophysical properties. Chem
Senses 1984;9:143-55.
17. Budavari S. The Merck Index - An Encyclopedia of Chemicals, Drugs,
and Biologicals. 12
ed. New Jersey: Merck and Co.; 1996. p. 1286.
18. Sills TL, Greenshaw AJ, Baker GB, Fletcher PJ. The potentiating
th
effect of sertraline and fluoxetine on amphetamine induced locomotor
activity is not mediated by serotonin. Psychopharmacology (Berl)
1999;143(4):426-32.
19. Ronsisvalle G, Marrazzo A, Prezzavento O, Cagnotto A, Mennini T,
Parenti C, et al. Opioid and sigma receptor studies. New developments
in the design of selective sigma ligands. Pure Appl Chem
2001;73:1499-509.
20. Lahon K, Pandian JJ, Lavakumar S. Effect of sub-acute administration
of propranolol on antidepressant effect ofalprazolam in albino mice.
Asian J Pharm Biol Res 2014;14 Suppl 2:240-4.
21. Vogel H. Drug Discovery and Evaluation Phamacological Essays.
2
ed. Heidelberg: Springer-Verlag; 2002. p. 561.
22. Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: A new
nd
method for screening antidepressants in mice. Psychopharmacology
(Berl) 1985;85(3):367-70.
23. Vogel H. Drug Discovery and Evaluation Phamacological Essays.
2
ed. Heidelberg: Springer-Verlag; 2002. p. 696.
24. Saxena AM, Mukherjee SK, Shukla G. Progress of Diabetes Research
nd
in India During 20
Century. New Delhi: National Institute of Science
and Communication (CSIR); 2006. p. 1-104.
th
25. Kulkarni SK. Heat and other physiological stress-induced analgesia:
Catecholamine mediated and naloxone reversible response. Life Sci
1980;27(3):185-8.
26. Huang W, Chen Z, Wang Q, Lin M, Wu S, Yan Q, et al. Piperine potentiates
the antidepressant-like effect of trans-resveratrol: Involvement of
monoaminergic system. Metab Brain Dis 2013;28(4):585-95.
27. DeVane CL, Liston HL, Markowitz JS. Clinical pharmacokinetics of
sertraline. Clin Pharmacokinet 2002;41(15):1247-66.
28. Kobayashi K, Ishizuka T, Shimada N, Yoshimura Y, Kamijima K,
Chiba K. Sertraline N-demethylation is catalyzed by multiple isoforms
of human cytochrome P-450 in vitro 1999;27(7):763-6.
29. Pentazocine. Br Med J 1970;2:409-11.
30. Anzenbacher P, Zanger UM. Metabolism of Drugs and Other
Xenobiotics. Weinheim, Germany: Wiley VCH; 2012. p. 420.
31. Khanuja SP, Arya JS, Srivastava SK. Antibiotic pharmaceutical
composition with lysergol as bioenhancer and method of treatment.
United States Patent Number 20070060604A1; 2007.
32. Lee KW, Everts H, Beynen AC. Essential oils in broiler nutrition. Int J
Poult Sci 2004;3(12):738-52.
33. Johri RK, Thusu N, Khajuria A, Zutshi U. Piperine-mediated changes in
the permeability of rat intestinal epithelial cells. The status of gammaglutamyl
transpeptidase
activity,
uptake of amino acids and lipid
peroxidation.
Biochem Pharmacol 1992;43(7):1401-7.
34. Khajuria A, Thusu N, Zutshi U. Piperine modulates permeability
characteristics of intestine by inducing alterations in membrane
dynamics: Influence on brush border membrane fluidity, ultrastructure
and enzyme kinetics. Phytomedicine 2002;9(3):224-31.
35. Singh J, Dubey RK, Atal CK. Piperine-mediated inhibition of
glucuronidation activity in isolated epithelial cells of the guinea-pig
small intestine: Evidence that piperine lowers the endogeneous UDPglucuronic
acid content. J
Pharmacol
Exp Ther
1986;236(2):488-93.
36. Reen RK, Roesch SF, Kiefer F, Wiebel FJ, Singh J. Piperine impairs
cytochrome P4501A1 activity by direct interaction with the enzyme and
not by down regulation of CYP1A1 gene expression in the rat hepatoma
5L cell line. Biochem Biophys Res Commun 1996;218(2):562-9.
37. Sambaiah K, Srinivasan K. Influence of spices and spice principles on
hepatic mixed function oxygenase system in rats. Indian J Biochem
Biophys 1989;26(4):254-8.
38. Volak LP, Ghirmai S, Cashman JR, Court MH. Curcuminoids inhibit
multiple human cytochromes P450, UDP-glucuronosyltransferase, and
sulfotransferase enzymes, whereas piperine is a relatively selective
CYP3A4 inhibitor. Drug Metab Dispos 2008;36(8):1594-605.
39. Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK,
Fromm MF. Piperine, a major constituent of black pepper, inhibits
human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther
2002;302(2):645-50.
Statistics
447 Views | 900 Downloads
How to Cite
Atal, S., P. Phadnis, S. Vyas, G. Gudsurkar, and R. Churihar. “EVALUATION OF THE INTERACTION OF PIPERINE WITH ANTIDEPRESSANT SERTRALINE AND ANALGESIC PENTAZOCINE, USING DIFFERENT ROUTES OF ADMINISTRATION IN ALBINO MICE”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 9, no. 1, Jan. 2016, pp. 193-7, https://innovareacademics.in/journals/index.php/ajpcr/article/view/9432.
Section
Original Article(s)