Journal of Bioequivalence & Bioavailability

Signalling pathways of cardiac hypertrophy

International Conference and Exhibiton on Pharmaceutical Regulatory Affairs

6-7 September 2011 Baltimore, USA

Rohini Agrawal

Posters: JBB

Abstract:

M itragyna speciosa is a local plant originated from Th ailand and Malaysia that has been used in the folk medicine for its morphine ?like eff ect mainly to ameliorate the abstinence period following weaning the morphine-addicted off as well as to relieve pain. Scientifi cally proven for possessing analgesic eff ect, there is lacking of data on the therapeutic index for the extract of the plant as well as mitragynine as the main alkaloid compound for further clinical use as a safe alternative of morphine substitute in addiction treatment. Th erefore, the aim of this study is to evaluate the therapeutic index of Malaysian M. speciosa and mitragynine and comparing with that of morphine. Five doses of alkaloid extract (20, 50, 160, 320, and 400 mg/ kg, p.o) and fi ve equivalent doses of mitragynine (4.2, 10.5, 33.6, 67.2, and 84 mg/kg, p.o.) were evaluated for analgesic activity using hot plate test and the ED 50 s as well as relative potency for the extract and mitragynine were compared with morphine (2.5-10 mg/kg, s.c.). LD 50 s of the extract and mitragynine were also estimated by acute toxicity up-and-down- procedure and further therapeutic indices of both test substances were calculated and compared with morphine. Both alkaloid extract (ED 50 =194.4 mg/kg) and mitragynine (ED 50 = 21.96 mg/kg) signifi cantly and dose-dependently showed analgesic eff ect compared to morphine (ED 50 =3.69 mg/kg). In addition, based on the acute toxicity study the LD 50 for alkaloid extract and mitragynine was estimated 591.6 mg/kg and 477mg/kg. Th e calculated therapeutic index for mitragynine was 7 times more than that of alkaloid extract and 7 times less than that of morphine.Although the alkaloid extract of M. speciosa was found far more toxic than morphine, the pure major compound of this plant, mitragynine, was relatively safe compared to morphine and can be a suitable alternative for further clinical studies on morphine addiction treatment.