Article Sidebar

Submitted
May 21, 2021
Published
May 21, 2021
Download
PDF
Statistic
Read Counter : 40 Download : 43

Main Article Content

Abstract

Objective


Dihydropyridines such as cilnidipine and amlodipine have been shown to block not only L-type but also N- type calcium channels. Ketorolac, a peripherally acting NSAID analgesic & tramadol, a centrally acting opioid analgesic are equipotent in treatment of mild to moderate acute pain. This study proposes to find any possible antinociceptive action of amlodipine and whether it potentiates analgesic activity of ketorolac and tramadol.


Methods


Adult healthy Wistar albino rats were grouped into 16 groups. The experiment was carried out using tail- flick method by analgesiometer. Different doses of amlodipine (2.5, 3, 3.5 mg/kg), ketorolac (15, 30, 45 mg/kg) and tramadol (10, 25, 50 mg/kg) and were administered intraperitoneally to select nonanalgesic doses. Different doses of amlodipine was combined with nonanalgesic doses of ketorolac & tramadol to study antinociceptive effect of combinations.


Results


Ketorolac and tramadol showed dose dependent antinociception which peaked at 2 hours. Amlodipine alone showed antinociceptive action at a dose of 3.5 mg/kg after 6 hour of administration. Higher doses of amlodipine (3, 3.5 mg/kg) in combination with nonanalgesic dose of tramadol produced significant antinociception. But Amlodipine at all dose potentiated the antinociceptive action of subanalgesic dose of ketorolac.


Discussion and conclusion


It can be concluded that amlodipine at high dose produced antinociceptive action. Combination of amlodipine with ketorolac and tramadol produced significant enhancement of antinociceptive activity of both tramadol & ketorolac in dose dependent manner.

Keywords

N-type calcium channel Amlodipine Analgesia

Article Details

How to Cite
K Saha, R Agrawal, & S Mohapatra. (2021). Amlodipine Potentiates Antinociceptive Activity of Ketorolac and Tramadol – An Experimental Study. International Journal of Research in Pharmacology & Pharmacotherapeutics, 5(2), 184-191. https://doi.org/10.61096/ijrpp.v5.iss2.2016.184-191
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX

References

  1. [1]. Gillis JC, Brogden RN. Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs 53(4), 1997, 139-88.
  2. [2]. Picard P, Bazin JE, Conio N, Ruiz F, Schoffler P. Ketorolac potentiates morphine in postoperative patient-controlled analgesia. Pain 73 (4), 1997, 401- 6.
  3. [3]. Chiaretti A, Simeone E, Langer A, Butera G, Piastra M, Tortorolo L, Polidori G. Analgesic efficacy of ketorolac and fentanyl in pediatric intensive care. Pediatr Med Chir 19(6), 1997, 419-24.
  4. [4]. Uphouse LA, Welch SP, Ward CR, Ellis EF, Embrey JP. Antinociceptive activity of intrathecal ketorolac is blocked by the k-opioid receptor antagonist, nor-binaltorphimine. Eur J Pharmacol 21(242), 1993, 53- 8
  5. [5]. Rooks WH, The pharmacologic activity of ketorolac tromethamine. Pharmacotherapy 10(4), 1990, 30S-2S.
  6. [6]. Vickers MD, O’ Flaherty D, Szekely SM, ReadM, Yoshizumi J. Tramadol: Pain relief by an opioid without depression of respiration. Anaesthesia. 47(4), 1992, 291-6. [PubMed: 1519677]
  7. [7]. Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M and Yamanaka M (1997) Voltage and pH dependent block of cloned N-type Ca21 channels by amlodipine. Br J Pharmacol 121, 1136–1140.
  8. [8]. Fujii S, Kameyama K, Hosono M, Hayashi Y and Kitamura K (1997) Effect of cilnidipine, a novel dihydropyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons. J Pharmacol Exp Ther 280, 1184–1191.
  9. [9]. Scholz H (1997) Pharmacological aspects of calcium channel blockers. Cardiovasc Drugs Ther 10 (Suppl 3):869–872.
  10. [10]. Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, et al . Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur J Pharmacol 419(4), 2001, 175-81
  11. [11]. http://www.hopkinsmedicine.org/neurology_neurosurgery/education/blaustein_pain/pain_research_core/quant_behavior.html
  12. [12]. Doğrul A, Yeşilyurt O, Deniz G, Işimer A. Analgesic effects of amlodipine and its interaction with morphine and ketorolac-induced analgesia. Gen Pharmacol. 29 (5) 1997, 839–45. [PubMed: 9347336]
  13. [13]. Maves Tj, Pechman PS, meller ST, Gebhart GF. Ketorolac potentiates morphine antinociception during visceral nociception in the rat. Anesthesiology 80(4), 1994, 1094-101.
  14. [14]. Omote K, Sonoda H, Kawamata M, Iwasaki H, Namiki A. Potentiation of antinociceptive effect of morphine by calcium channel blockers at the level of the spinal cord. Anesthesiology. 1993 Oct;79(4):746–52.[PubMed: 8214754]
  15. [15]. Omote K, Kawamata M, Satoh O, Iwasaki H, Namiki A. Spinal antinociceptive action of an N- type voltage-dependent calcium channel blocker and the synergistic interaction with morphine. Anaesthesiology. 84 (3), 1996, 636– 43. [PubMed: 8659792]
  16. [16]. Del Pozo E, Caro G, Baeyens JM. Analgesic effects of several calcium channel blockers in mice. Eur J Pharmacol. 137(4), 1987, 155–60. [PubMed: 3609138]
  17. [17]. Lia EN, Prado WA. Effects of intrathecal L- and N- type calcium channel blockers on the antinociception evoked by opioid agonists in the rat tail flick test. Acta Physiol Pharmacol Ther Latinoam. 49 (4), 1999, 195–203.