naloxone and Psychomotor-Agitation

Five patients with either acute or tardive neuroleptic-induced akathisia (5 weeks to 1 1/2 years duration) were videotaped before, during, and after a 2-week trial of propoxyphene (Darvon), 100 mg q.i.d., or acetaminophen (Tylenol) with 30 mg codeine, two tabs, q.i.d. Three "blinded" observers, experienced in movement disorders, rated the involuntary movements shown on the videotapes and agreed that, on opioids, all patients showed substantial to complete improvement of their stereotyped restless akathitic movements. Matching placebo was not beneficial. One patient who had improved on opioids was challenged with naloxone while on the opioids. There was a brief but severe reactivation of the akathisia. Our results suggest that opioids offer a selective therapy for patients with neuroleptic-induced akathisia and further suggest that the endogenous opiate system may be involved in patients with neuroleptic-induced akathisia.

Topics: Acetaminophen; Adult; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Codeine; Dextropropoxyphene; Female; Humans; Male; Middle Aged; Naloxone; Psychomotor Agitation; Receptors, Opioid

Topics: Administration, Intranasal; Adult; Drug Overdose; Female; Humans; Naloxone; Narcotic Antagonists; Psychomotor Agitation

Previous studies have uncovered a potential role of the opioid system in iron hemostasis and dopamine metabolism. Abnormalities in both of these systems have been noted in human RLS. Autopsy studies of human RLS have shown an endogenous opioid deficiency in the thalamus. Opioids, particularly prolonged-release oxycodone/naloxone, have been approved in Europe to be a second-line therapy for severe restless legs syndrome (RLS). To study the role of opioid receptors in the pathogenesis of RLS, we used a triple knockout (KO) mouse strain that lack mu, delta, and kappa opioid receptors and explored the behavioral and biochemical parameters relevant to RLS. The triple KO mice showed hyperactivity and a trend of increased probability of waking during the rest period (day) akin to that in human RLS (night). Surprisingly, triple KO mice also exhibit decreased serum iron concentration, evidence of anemia, a significant dysfunction in dopamine metabolism akin to that noted in human RLS, as well as an increased latency in response to thermal stimuli. To our knowledge, this is the first study to demonstrate that the endogenous opioid system may play a role in iron metabolism and subsequently in the pathogenesis of anemia. It is also the first study showing that opioid receptors are involved in the production of motor restlessness with a circadian predominance. Our findings support the role of endogenous opioids in the pathogenesis of RLS, and the triple KO mice can be used to understand the relationship between iron deficiency, anemia, dopaminergic dysfunction, and RLS.

Topics: Analgesics, Opioid; Anemia; Anemia, Iron-Deficiency; Animals; Dopamine; Dopaminergic Neurons; Iron; Iron Deficiencies; Male; Mice; Mice, Knockout; Naloxone; Opioid Peptides; Psychomotor Agitation; Receptors, Opioid, mu; Restless Legs Syndrome

Topics: Aged; Aged, 80 and over; Delirium; Female; Hospitalization; Humans; Male; Middle Aged; Naloxone; Pilot Projects; Psychomotor Agitation; Stroke

The effect of non-benzodiazepine anxiolytics on the ethanol-induced hyperlocomotion and behavioral sensitization was assessed in male DBA/2 mice. Selank that enhances activity of the endogenous opioid system (0.3 mg/kg, intraperitoneally), similar to the nonselective opiate receptor blocker naloxone (1.0 mg/kg, intraperitoneally), prevented the development of ethanol-induced (2.0 g/kg intraperitoneally) hyperlocomotion, in contrast to σ1-receptors agonist Afobazole (1.0 mg/kg, intraperitoneally) that did not inhibit ethanol-induced behavioral stimulation. Single dose of Selank significantly blocked manifestation of motor sensitization without affecting its formation. These findings suggest that Selank can modulate the motivational effects of ethanol.

Topics: Akathisia, Drug-Induced; Animals; Anti-Anxiety Agents; Behavior, Animal; Benzimidazoles; Ethanol; Injections, Intraperitoneal; Male; Mice; Mice, Inbred DBA; Morpholines; Naloxone; Narcotic Antagonists; Oligopeptides; Psychomotor Agitation; Receptors, Opioid

Our previous studies have indicated that the thalamic nucleus submedius (Sm) is involved in modulation of nociception and plays an important role in an endogenous analgesic system (a feedback loop) consisting of spinal cord-Sm-ventrolateral orbital cortex-periaqueductal gray-spinal cord. To investigate whether opioids are involved in this antinociception pathway, the effects of microinjection of morphine and naloxone into the Sm on the nociceptive behavior (agitation) evoked in the formalin test were investigated in the awake rat using an automated movement detection system. The results indicate that a unilateral microinjection of morphine (5 micro g, 0.5 microl) into the Sm suppresses the formalin-induced agitation response, but does not influence spontaneous motor activity, and that the morphine-induced depression can be reversed by microinjection of the opioid receptor antagonist naloxone (1.0 micro g, 0.5 microl) into the same Sm site. The results suggest that opioid receptors in the Sm may be involved in the Sm-mediated depression of persistent inflammatory pain.

Topics: Afferent Pathways; Animals; Behavior, Animal; Efferent Pathways; Female; Male; Microinjections; Morphine; Naloxone; Narcotic Antagonists; Neural Inhibition; Nociceptors; Opioid Peptides; Pain; Pain Measurement; Pain Threshold; Posterior Thalamic Nuclei; Psychomotor Agitation; Rats; Rats, Sprague-Dawley; Receptors, Opioid