Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats.

Abstract

RATIONALE:

A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine self-administration.

OBJECTIVES:

The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine self-administration would reduce opiate self-administration.

METHODS:

Amitifadine, a triple reuptake inhibitor of dopamine, norepinephrine, and serotonin, was assessed in female Sprague-Dawley rats to determine whether it significantly reduces remifentanil self-administration with either acute or chronic treatment.

RESULTS:

Acutely, amitifadine doses of 5, 10, and 20 mg/kg each significantly reduced remifentanil self-administration. In a chronic study, repeated treatment with 10 mg/kg of amitifadine continued to reduce remifentanil self-administration, even after the cessation of treatment. However, amitifadine was not found to attenuate the rise in remifentanil self-administration with continued access. This study and our earlier one showed that the 10 mg/kg amitifadine dose did not significantly affect food motivated responding. Amitifadine did not attenuate remifentanil-induced antinociception as measured on the hot plate test but extended and maintained antinociceptive effects.

CONCLUSIONS:

These studies show the promise of amitifadine as a treatment for countering opiate self-administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain.

• Authors: Edward D Levin, Corinne Wells, Andrew Hawkey, Zade Holloway, Graham Blair, Alexander Vierling, Ashley Ko, Caroline Pace, John Modarres, Anthony McKinney, Amir H Rezvani, Jed E Rose
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 237 Issue 6 Pg. 1681-1689 (Jun 2020) ISSN: 1432-2072 [Electronic] Germany
• PMID: 32125484 (Publication Type: Journal Article)

Chemical References

• 1-(3,4-dichlorophenyl)-3-azabicyclo-(3.1.0)hexane hydrochloride
• Analgesics, Opioid
• Aza Compounds
• Bridged Bicyclo Compounds, Heterocyclic
• Dopamine Uptake Inhibitors
• Serotonin Uptake Inhibitors
• Serotonin
• Nicotine
• Remifentanil
• Dopamine
• Norepinephrine

Topics

• Analgesics, Opioid (administration & dosage)
• Animals
• Aza Compounds (pharmacology, therapeutic use)
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology, therapeutic use)
• Dopamine (metabolism)
• Dopamine Uptake Inhibitors (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Humans
• Motivation (drug effects, physiology)
• Nicotine (administration & dosage)
• Norepinephrine (antagonists & inhibitors, metabolism)
• Pain (drug therapy, metabolism)
• Rats
• Rats, Sprague-Dawley
• Remifentanil (administration & dosage)
• Self Administration
• Serotonin (metabolism)
• Selective Serotonin Reuptake Inhibitors (pharmacology, therapeutic use)
• Stereoisomerism