Search Results

1 - 2 of 2 items

  • Author: Shiv Gupta x
Clear All Modify Search
Synthesis and biological evaluation of some novel 1-substituted fentanyl analogs in Swiss albino mice

ABSTRACT

Fentanyl [N-(1-phenethyl-4-piperidinyl)propionanilide] is a potent opioid analgesic agent, but a has narrow therapeutic index. We reported earlier on the synthesis and bioefficacy of fentanyl and its 1-substituted analogs (1-4) in mice. Here we report the synthesis and biological evaluation of four additional analogs, viz. N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), N-tbutyl- 3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6), isopropyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (7) and t-butyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (8). The median lethal dose (LD50) determined by intravenous, intraperitoneal and oral routes suggests these analogs to be comparatively less toxic than fentanyl. On the basis of observational assessment on spontaneous activities of the central, peripheral, and autonomic nervous systems, all the analogs were found to be similar to fentanyl. Naloxone hydrochloride abolished the neurotoxic effects of these analogs, thereby ascertaining their opioid receptor-mediated effects. All the analogs displayed significant analgesic effects, measured by formalin-induced hind paw licking and tail immersion tests at their respective median effective dose (ED50). They also exhibited 8-12 fold increase in therapeutic index over fentanyl. However, 5 and 6 alone produced lower ED50 (20.5 and 21.0 μg/kg, respectively) and higher potency ratio (1.37 and 1.33, respectively) compared to fentanyl. They could thus be considered for further studies on pain management

Open access
Thermally assisted OSL: A potent tool for improvement in minimum detectable dose and extension of dose range of Al2O3:C

Abstract

The influence of electron-phonon interaction on the shape of the optically stimulated luminescence decay curve of Al2O3:C has been studied using thermally assisted optically stimulated luminescence (TA-OSL). The minimum detectable dose (MDD) of a phosphor depends on the standard deviation of the background signal which affects the signal-to-noise ratio. The standard deviation of the background signal reduces at lower stimulation light intensity while the readout time increases. Further, measurement at higher temperature enhances the OSL signal with faster decay due to the temperature dependence of photo-ionization cross-section. To achieve the same decay constant and more signal, the temperature of measurement was raised. As a result of lowering the stimulation in-tensity at higher temperature (85°C) the overall MDD of α-Al2O3:C was found to improve by 1.8 times. For extension of dose linearity in higher range, deeper traps were studied by simultaneous application of CW-OSL and thermal stimulation up to 400°C, using a linear heating rate of 4K/s. By using this method, two well defined peaks at 121°C and 232°C were observed. These TA-OSL peaks have been correlated with two deeper defects which can be thermally bleached at 650°C and 900°C respectively. These deeper defects are stable up to 500°C, so they can store absorbed dose information even if the sample is inadvertently exposed to light or heat. The dose vs. TA-OSL response from deep traps of α-Al2O3:C was found to be linear up to 10 kGy, thus extending its application for high dose dosimetry.

Open access