naloxone and Movement-Disorders

Topics: Acute Disease; Cerebrovascular Disorders; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Movement Disorders; Naloxone; Random Allocation

Blocking dopamine (DA) receptors in the basal ganglia can cause parkinsonian symptoms, acute dystonia, akathisia, tardive dyskinesia (TD), and neuroleptic malignant syndrome. TD is characterized by abnormal, involuntary, irregular motor movements involving muscles of the head, limbs, or trunk. Many drug therapies have been tried for TD, but none are approved by the U.S. Food and Drug Administration. The second-generation antipsychotic drugs should be considered as a treatment of first choice for clinically significant TD, because they will also be potentially effective as a primary treatment for the underlying disorder. Dopamine-depleting drugs are effective for TD, but their practical use is severely limited because of tolerability and safety concerns. Various DA-modulating drugs have been tried; clinical evidence of efficacy suggests that amantadine (Symmetrel®) and naloxone (Narcan®) are worthwhile to try. Although efficacy evidence for buspirone (Buspar®) in TD is limited, this drug is safe and well tolerated and would be reasonable to try. Bromocriptine (Parlodel®), selegiline (Deprenyl®), and cholinergic-modulating drugs are not considered effective for TD.

Topics: Amantadine; Antipsychotic Agents; Buspirone; Dopamine Agents; Dyskinesia, Drug-Induced; Humans; Movement Disorders; Naloxone; Narcotic Antagonists; Serotonin Receptor Agonists

Dyskinesias and seizures are both medically refractory disorders for which cannabinoid-based treatments have shown early promise as primary or adjunctive therapy. Using the Borna disease (BD) virus rat, an animal model of viral encephalopathy with spontaneous hyperkinetic movements and seizure susceptibility, we identified a key role for endocannabinoids in the maintenance of a balanced tone of activity in extrapyramidal and limbic circuits. BD rats showed significant elevations of the endocannabinoid anandamide in subthalamic nucleus, a relay nucleus compromised in hyperkinetic disorders. While direct and indirect cannabinoid agonists had limited motor effects in BD rats, abrupt reductions of endocannabinoid tone by the CB1 antagonist SR141716A (0.3 mg/kg, i.p.) caused seizures characterized by myoclonic jerks time-locked to periodic spike/sharp wave discharges on hippocampal electroencephalography. The general opiate antagonist naloxone (NLX) (1 mg/kg, s.c.), another pharmacologic treatment with potential efficacy in dyskinesias or L-DOPA motor complications, produced similar seizures. No changes in anandamide levels in hippocampus and amygdala were found in convulsing NLX-treated BD rats. In contrast, NLX significantly increased anandamide levels in the same areas of normal uninfected animals, possibly protecting against seizures. Pretreatment with the anandamide transport blocker AM404 (20 mg/kg, i.p.) prevented NLX-induced seizures. These findings are consistent with an anticonvulsant role for endocannabinoids, counteracting aberrant firing produced by convulsive agents, and with a functional or reciprocal relation between opioid and cannabinoid tone with respect to limbic convulsive phenomena.

Topics: Animals; Anticonvulsants; Arachidonic Acids; Basal Ganglia; Borna Disease; Cannabinoid Receptor Modulators; Convulsants; Disease Models, Animal; Endocannabinoids; Limbic System; Male; Movement Disorders; Naloxone; Narcotic Antagonists; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Inbred Lew; Receptor, Cannabinoid, CB1; Rimonabant; Seizures

We assessed the withdrawal intensity in acutely morphine-dependent mice using a pretreatment with escalating doses of naloxone. All animals received a single dose of morphine (100 mg/kg) for the induction of acute opioid dependency. Group 1 (control) received three injections of normal saline and then naloxone 0.8 mg/kg. Group 2 received increasing pretreatment doses of naloxone (0.1, 0.2, and 0.4 mg/kg) and a challenge dose of 0.8 mg/kg. Group 3 received three injections of naloxone 0.1 mg/kg and a challenge dose of 0.8 mg/kg. Groups 4 and 5 were used to verify whether ED(50) found in previous studies was comparable with values obtained in the current experiments. The withdrawal intensity was determined by the number of jumps. The mice of group 1 exhibited significantly more jumps after 0.8 mg/kg of naloxone as compared with group 2. The number of jumps in response to naloxone between groups 1 and 2 and groups 2 and 3 was not significantly different. The results show that pretreatment with increasing naloxone doses significantly reduced the withdrawal intensity as compared with the control group; whereas pretreatment with repeated low antagonist did not reduce it significantly.

Topics: Animals; Behavior, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Male; Mice; Morphine; Morphine Dependence; Movement Disorders; Naloxone; Narcotic Antagonists; Substance Withdrawal Syndrome

In the present study, effect of cholecystokinin (CCK) agonists and on dependence to morphine in mice has been investigated. The influence of dopaminergic, adrenergic, cholinergic and serotonergic on attenuation of naloxone-induced jumping in morphine-dependent mice by CCK agonists were also considered. Mice were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 a.m. 1 p.m. and 4 p.m.) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the 4th day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2 hr after the last dose of morphine. To study effects of CCK receptor agonists, 10 injection of morphine (3 administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. The CCK agonists CCK-8 (0.001-0.1 mg/kg), unsulfated CCK-8 (CCK-8U; 0.001-0.1 mg/kg) and caerulein (0.00001-0.01 mg/kg) were able to prevent withdrawal signs precipitated by naloxone (5 mg/kg). Sulpiride and pimozide increased response induced by CCK-8 agonists. The dopamine antagonists also attenuates jumping by themselves. SCH 23390 did not alter the CCK-8 effect, but decreased the jumping by itself. Phenoxybenzamine, propranolol, methysergide and atropine did not change the caerulein effect significantly. However, single administration of atropine increased and methysergide decreased jumping. It is concluded that CCK mechanism(s) may be involved in morphine dependence, and dopaminergic mechanism(s) may interact with CCK in attenuation of naloxone-induced jumping.

Topics: Adrenergic Antagonists; Animals; Atropine; Benzazepines; Ceruletide; Dopamine Antagonists; Male; Methysergide; Mice; Morphine; Morphine Dependence; Movement Disorders; Muscarinic Antagonists; Naloxone; Narcotic Antagonists; Phenoxybenzamine; Pimozide; Propranolol; Receptors, Cholecystokinin; Serotonin Antagonists; Sincalide; Substance Withdrawal Syndrome; Sulpiride

Stroke is an infrequent but recognized complication of heroin addiction. Two heroin addicts, aged 34 and 19 years, developed ballistic movements after intravenous heroin overdose. Patient 1 presented bilateral ballism 1 week after intravenous heroin injection. Magnetic resonance imaging (MRI) showed bilateral ischemic lesions of the globus pallidus, suggesting a generalized cerebral hypoxia during the comatose state as pathogenic mechanism. Patient 2 presented an acute left hemiballismus when consciousness was restored with naloxone. MRI demonstrated an ischemic infarct in the right striatum. An embolic mechanism of stroke was suspected in this patient, considering the normal results of blood analysis, echocardiogram and cerebral arteriograms. Ballistic movements ceased after administration of haloperidol; both patients remained without abnormal movements thereafter.

Topics: Adult; Anti-Dyskinesia Agents; Basal Ganglia; Brain Ischemia; Coma; Corpus Striatum; Drug Overdose; Globus Pallidus; Haloperidol; Heroin; Humans; Magnetic Resonance Imaging; Male; Movement Disorders; Naloxone; Narcotic Antagonists; Substance Abuse, Intravenous; Tomography, X-Ray Computed

The possibility that activation of opioid receptors is involved in the analgesic activity of ketorolac was explored. The analgesic effects of ketorolac, of ketocyclazocine, the prototype kappa-agonist, and of morphine, the prototype mu-agonist, were assayed in the pain-induced functional impairment model in the rat. All three drugs induced a significant analgesic effect in this model. Naloxone was able to antagonize the effects of ketocyclazocine and morphine. However, the effect of ketorolac was not blocked by naloxone, although a high dose, 3.2 mg kg-1, capable of blocking kappa-receptors was used. It is concluded that activation of mu- or kappa-opioid receptors, by either a direct or an indirect mechanism, does not play a role in the analgesic activity of ketorolac.

Topics: Analgesics; Analgesics, Non-Narcotic; Animals; Ethylketocyclazocine; Female; Ketorolac; Morphine; Movement Disorders; Naloxone; Pain Measurement; Rats; Rats, Wistar; Receptors, Opioid, kappa; Receptors, Opioid, mu; Time Factors; Tolmetin

Dyskinetic, writhing-like movements, similar to those produced in mice after an intraperitoneal (IP) injection of acetic acid, were elicited by intrathecal (IT) injection of GABA, glycine, taurine or beta-alanine. Baclofen and muscimol failed to produce this behavior. While acetic acid-induced writhing is inhibited by narcotic and nonnarcotic compounds, GABA-induced writhing was found to be insensitive to pretreatment with either morphine or capsaicin. Moreover, acetic acid-induced writhing does not appear to involve GABAergic transmission as IT injections of nipecotic acid did not alter the intensity of response to IP acetic acid while it enhanced the response to IT GABA. Writhing induced by glycine was not inhibited by strychnine at subconvulsive doses, suggesting that it involves an action at strychnine-insensitive receptors. Together these data suggest that while the dyskinetic movements produced by inhibitory amino acids do not appear to reflect an alteration in nociception, they may mimic either the motor response to abdominal pain or spasticity.

Topics: Alanine; Animals; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Glycine; Injections, Intraperitoneal; Injections, Spinal; Male; Mice; Morphine; Movement Disorders; Naloxone; Strychnine; Taurine; Time Factors

Topics: Brain Ischemia; Echoencephalography; Humans; Movement Disorders; Naloxone; Neurosurgery; Retrospective Studies

Topics: Aged; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Levodopa; Male; Middle Aged; Movement Disorders; Muscle Rigidity; Naloxone; Parkinson Disease; Receptors, Dopamine

Topics: Animals; Catatonia; Humans; Male; Medulla Oblongata; Morphine; Movement Disorders; Naloxone; Pain; Rats; Rats, Inbred Strains

Less than Glu-His-Pro-OH or 'acid' TRH, until now considered to be an inactive metabolite of TRH, induces in rats when administered intracerebroventricularly (i.c.v.), stereotyped behavior and, from 12.5 micrograms, wet-dog shakes (WDS). WDS induced by 200 micrograms less than Glu-His-Pro-OH are antagonized by apomorphine, haloperidol and cyproheptadine while phentolamine and naloxone are without effect. For this action 'acid' TRH appears as effective as TRH itself and might have the same mechanism.

Topics: Animals; Apomorphine; Cyproheptadine; Dose-Response Relationship, Drug; Haloperidol; Injections, Intraventricular; Male; Movement Disorders; Naloxone; Phentolamine; Pyrrolidonecarboxylic Acid; Rats; Rats, Inbred Strains; Thyrotropin-Releasing Hormone

Topics: Animals; Corpus Striatum; Dopamine; Dose-Response Relationship, Drug; Female; Mice; Morphine; Movement Disorders; Naloxone; Rats; Rotation; Time Factors