Acute motor effects induced by opioid antagonists in Parkinson’s disease: could naloxone be a rescue therapy?

Abstract

Endogenous opioid system is a highly complex system. Since his main role consists in pain and mood regulation, opioids current use in clinical practice is principally linked to analgesia. However, opioid receptors and endogenous ligand are diffusely distributed in the central nervous system and opioid peptides act as neurotransmission modulators in basal ganglia. Indeed, starting from the 1970s of the last century, some studies reported that the opiate peptide beta endorphin could inhibit the release of dopamine from the striatum [1] and intrathecal infusion of beta endorphin in rats produced muscular rigidity counteracted by the opiate antagonist naloxone [2]. Furthermore, in patients with Parkinson’s disease (PD), naloxone could improve some parkinsonian motor features or the “rigidity phase,” as demonstrated by Agnoli and coll. [3] and Trabucchi and coll. [4]. Nevertheless, other studies observed no effects of opiate antagonism on movement disorders [5], and despite the reported earlier findings, the interest in antiparkinsonian effect of opioid antagonist decreased over time. Anyway, bearing in mind the possible antiparkinsonian effect of naloxone, one of us (G.B.) searched for an acute response after naloxone administration in PD patients in “off” conditions. We presented a series of video cases supporting the potential role of opioid antagonists as effective treatment in improving motor conditions in PD patients. Video cases Patient No. 1.Man, 62 years old, with a disease duration of 10 years. At the time of evaluation, he had L-dopa responsive parkinsonismwith motor fluctuations. “Off”motor conditions were characterized by severe generalized bradykinesia, “Pisa syndrome”with abnormal trunk deviation and severe freezing of gait. Rest tremor of the left upper arm was also present. Clinical evaluations were performed before and 30 min after the intravenous infusion of naloxone 0.3 mg, after 12-h fasting from antiparkinsonian therapy. Naloxone administration produced an important improvement of gait, characterized by higher speed with reduction in freezing of gait episodes, especially on turning. Mild dyskinesias of the left arm were also observed. Patient No. 2. Man, 47 years old. Previous exposure to pesticides and disease duration of 12 years. “Off” motor conditions were characterized by severe generalized bradykinesia and rigidity with a left-side predominance. Clinical evaluations were performed before and 30 min after the intravenous infusion of naloxone 0.3 mg, after an overnight fasting from L-dopa. After naloxone administration, there was an improvement of bradykinesia and rigidity, with drug-induced choreo-athetotic dyskinetic movements affecting left upper limb together with a dystonic posture of the left leg. Patient No. 3. Man, unknown age, unknown symptoms onset, visited in Ethiopia by G.B. He was never treated with antiparkinsonian medication. “Off” motor conditions were characterized by severe generalized bradykinesia and rigidity, stooped posture, shuffling gait, upper limb rest tremor. He was unable to stand and walk unassisted. After naloxone administration, the patient was able to stand without help and to walk at a higher speed. We clinically evaluated three patients, affected by PD, before and after acute intravenous infusion of naloxone 0.3 mg * Mario Zappia [email protected]