Fentanyl-related substances elicit antinociception and hyperlocomotion in mice via opioid receptors.

Synthetic opioids have been implicated as the single greatest contributor to rising drug-related fatalities in recent years. This study evaluated mu-opioid receptor (MOR) mediated effects of seven fentanyl-related substances that have emerged in the recreational drug marketplace, and for which there are no existing or only limited in vivo data. Adult male Swiss Webster mice were administered fentanyl-related substances and their effects on nociception and locomotion as compared to MOR agonist standards were observed.

Methylnaltrexone crosses the blood-brain barrier and attenuates centrally-mediated behavioral effects of morphine and oxycodone in mice.

Background: Antagonism of peripheral opioid receptors by methylnaltrexone (MNTX) was recently proposed as a potential mechanism to attenuate the development of opioid analgesic tolerance based on experiments conducted in mice. However, reports indicate that MNTX is demethylated to naltrexone (NTX) in mice, and NTX may subsequently cross the blood-brain barrier to antagonize centrally-mediated opioid effects. The goal of this study was to determine whether MNTX alters centrally-mediated behaviors elicited by the opioid analgesics, morphine and oxycodone, and to quantify concentrations of MNTX and NTX in blood and brain following their administration in mice.

Opioid-like antinociceptive and locomotor effects of emerging fentanyl-related substances.

The emergence of several fentanyl-related substances in the recreational drug marketplace has resulted in a surge of opioid overdose deaths in the United States. Many of these substances have never been examined in living organisms under controlled conditions. In the present study, seven fentanyl-related substances were tested in adult male Swiss Webster mice for their effects on locomotion and antinociception and compared to those of fentanyl and morphine.

Oxycodone-like discriminative stimulus effects of fentanyl-related emerging drugs of abuse in mice.

Background: Fentanyl and its structurally related compounds have emerged as the most significant contributors to opioid overdose fatalities in recent years. While there is abundant information about the pharmacological effects of fentanyl, far less is known of its more recently abused analogs. The objective of this study was to determine whether fentanyl and several fentanyl-related substances would engender oxycodone-like responding in a mouse model of oxycodone discrimination.