Intravenously and iontophoretically administered naloxone reverses ischemic changes in rat hippocampus.

Abstract

Forty rats under urethane anesthesia were subjected to cerebral ischemia by ligation of the right carotid, the right plus the left carotid, or the right carotid plus two vertebral arteries. Ischemia caused three types of changes in the field potential of the right hippocampal CA1 region evoked by fimbrial stimulation: 1) completely reversible deterioration (57% and 16% of the rats with unilateral and bilateral carotid artery ligation, respectively), 2) moderate deterioration (37% and 24% of the rats with unilateral and bilateral carotid artery ligation) and 3) irreversible loss of the evoked activity (6% and 60% of the rats with unilateral and bilateral carotid artery ligation and all the rats subjected to three-vessel occlusion). Naloxone improved the moderate deterioration in 10 of 11 rats (1-3 mg/kg i.v.) and in 15 of 16 (50-150 nA) iontophoretic applications, but naloxone did not restore the lost evoked activity. Intravenous morphine (10 mg/kg) aggravated the ischemic changes, and this effect was reversed by naloxone, while iontophoretic administration of morphine caused only excitation. These findings suggest that naloxone has a favorable effect on cerebral ischemia not severe enough to cause transmission failure. The reversal of ischemic changes by iontophoretic naloxone indicates that its site of action is at the neuronal or microcirculatory level. (Stroke 1989;20:1059-1064

Naloxone’s displacement of [11C]carfentanil and duration of receptor occupancy in the rat brain: implications for opioid overdose reversal

“…Positron emission tomography (PET) and the MOR radioligand, [ 11 C]CFN have been used to measure blockade of MOR by NLX non-invasively in humans [20] and in non-human primates [21]. Most [ 11 C]CFN PET studies have assessed receptor occupancy (RO) within 10 min after an acute NLX dose for various administration methods [19,[22][23][24][25][26][27][28][29][30]. In particular, two relevent clinical reports have been published on NLX's clearance rate from MORs.…”

A double blind randomized pilot trial of naloxone in the treatment of acute ischemic stroke

“…electric neuronal function impairment?]. The administration of Naloxone was found to improve functional neurological deficit [3,7,22,40], cerebral blood flow [I 4, 34], and electrophysiological responses [14,12] in experimental models of focal ischemia. The administration of Naloxone was found to improve functional neurological deficit [3,7,22,40], cerebral blood flow [I 4, 34], and electrophysiological responses [14,12] in experimental models of focal ischemia.…”