chiniofon and Nervous-System-Diseases

Topics: Clioquinol; Humans; Hydroxyquinolines; Japan; Kinetics; Nervous System; Nervous System Diseases; Optic Atrophy; Spinal Cord Diseases

Clioquinol was administered to cats for more than 200 days, in order to investigate the neural mechanisms underlying the sensory disturbances of subacute myelo-opticoneuropathy (SMON). Electrophysiological examination, carried out under urethane-chloralose anesthesia, revealed that there were 3 major abnormalities in the surface potentials of the nucleus gracilis evoked by sural nerve stimulation, i.e., a reduction in the peak-to-peak amplitude, prolongation of the N wave, and a reduction in P wave amplitude. The reduction in P-wave amplitude suggested suppression of presynaptic inhibition. This was confirmed by excitability tests of the presynaptic terminals of sural nerve fibers within the nucleus gracilis. Recordings of orthodromic volleys in the fasciculus gracilis, elicited by sural nerve stimulation, showed an increase in temporal dispersion. Increased temporal dispersion was also evident from recordings of antidromic volleys in the sural nerve. Peripheral axons of primary sensory neurons in the sural nerve and their terminals within the spinal cord showed no significant functional abnormalities in the chronic clioquinol cat. It is suggested that primary axons in the fasciculus gracilis near the nucleus gracilis are affected by chronic clioquinol administration.

Topics: Action Potentials; Animals; Cats; Clioquinol; Electric Stimulation; Hydroxyquinolines; Medulla Oblongata; Nervous System Diseases; Spinal Cord

The neurotoxicity of a combination of broxyquinoline and brobenzoxaldine (Intestopan Forte, containing 500 mg and 100 mg of the drugs respectively per capsule) was investigated by prospective clinical and electrophysiological studies in patients and volunteer subjects given the drugs in therapeutic doses (two capsules three times a day for 5 days). Of 16 patients with intestinal amoebiasis given the drugs (study A), 13 (81.25%) were cured. Adverse effects were mild and did not affect treatment. No neurological adverse effect was reported. Neurological examinations revealed no abnormality in any patient after treatment. Seven volunteer subjects underwent medical, neurological and ophthalmological examinations, and electrophysiological studies of ulnar and peroneal nerve conduction before and after treatment with the drugs in therapeutic doses (study B). Transient paresthesias were reported by one subject on the fourth day of treatment. No medical, neurological or ophthalmological abnormality was detected in any subject after treatment. There was no significant change in motor nerve conduction velocities. There was a significant (P less than 0.001) increase in the stimulus strength for distal ulnar stimulation and a significant (P less than 0.01) decrease in stimulus duration for proximal and distal ulnar stimulation. No significant changes were seen in the peroneal nerves in these parameters. No qualitative abnormality was seen in the oscilloscopic patterns of nerve conduction after treatment. Literature on the neurotoxicity of the halogenated hydroxyquinolines is reviewed. It is concluded that broxyquinoline and brobenzoxaldine (and probably other halogenated hydroxyquinolines as well) are safe and effective in therapeutic doses; neurotoxicity is unlikely to occur when these drugs are used according to therapeutic recommendations.

Topics: Adult; Drug Combinations; Dysentery, Amebic; Female; Heartburn; Humans; Hydroxyquinolines; Male; Middle Aged; Nausea; Nervous System Diseases; Neural Conduction; Oxyquinoline; Paresthesia; Peroneal Nerve; Physical Exertion; Prospective Studies; Pruritus; Quinaldines; Quinolines; Ulnar Nerve

Topics: Anti-Infective Agents; Drug Combinations; Eye Diseases; Humans; Hydroxyquinolines; Male; Middle Aged; Nervous System Diseases; Oxyquinoline

5-Chloro-7-iodo-8-hydroxy-quinoline (clioquinol) was found to induce a very marked increase in the concentration of 63Ni2+ in various tissues of mice when given orally together with the metal, compared with oral administrations of 63Ni2+ only. Markedly increased tissue concentrations, although less expressed than for the 63Ni2+, were also observed for 65Zn2+. Clioquinol increased the tissue levels of 203Hg2+ to a lesser extent. When clioquinol was given intraperitoneally and 63Ni2+ was given intravenously there were also very markedly increased tissue levels of the metal, compared with intravenous injections of 63Ni2+ only. It was also shown that the urinary excretion of 63Ni2+ was greatly increased in mice given the metal orally together with clioquinol, compared with mice given the 63Ni2+ only. Clioquinol and other 8-hydroxy-quinolines form lipophilic chelates with metallic cations and the observed effects on the tissue-disposition of the metals are probably due to a facilitated penetration through the cellular membranes. Determinations of the chloroform:water partition coefficients showed the highest lipophilicity for the nickel-clioquinol-complex followed in decreasing order by the complexes with zinc and mercury. These data suggest that the ability of the clioquinol to affect the uptake of the metals in the cells may be related to the relative lipophilicity of the metal-clioquinol-complexes. Clioquinol and other halogenated 8-hydroxy-quinolines are linked with the SMON-syndrom, which has been observed preferentially in Japan. It is suggested that the pathogenesis of SMON may involve an accumulation of toxic concentrations of metals in the tissues due to facilitated uptake by complex-formation with halogenated 8-hydroxy-quinolines.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Clioquinol; Female; Hydroxyquinolines; Mercury; Mice; Mice, Inbred C57BL; Nervous System Diseases; Nickel; Solubility; Tissue Distribution; Zinc

The investigation was undertaken to study the neurological symptoms in rats caused by maintaining high plasma concentration of about 30 nmol/ml or more, of clioquinol. Clioquinol suspension which was prepared using polysorbate 80 was administered intraperitoneally to rats and plasma and tissue concentrations were determined. On administration of clioquinol of 100 and 200 mg/kg, the mean plasma concentrations of clioquinol reached maximum values of 30 and 58 nmol/ml, respectively, after 0.5-1 h and thereafter decreased rapidly. With 400 mg/kg, however, plasma concentration reached maximum value of about 75 nmol/ml and fell slowly. By single and repeated administration of the suspension, clioquinol was distributed in the liver and kidney at a high concentration, and also in the nervous system. In experiments on appearance of neurotoxicity in rats by repeated administration of the suspension, all of 10 rats administered intraperitoneally with 100 mg/kg/d did not develop any neurological symptoms for about 30 d. On the other hand, one of 10 and 7 of 13 rats administered with 200 and 400 mg/kg/d, respectively, developed ataxia in the hind legs or all legs on the 3rd to the 12th day after starting administration. Pathologically, a slight change of the peripheral nerve, central chromatolysis of the anterior horn neuron and severe neuronal degeneration of the Ammon's horn were observed in the rats with ataxia.

Topics: Animals; Ataxia; Clioquinol; Hydroxyquinolines; Injections, Intraperitoneal; Male; Nervous System Diseases; Rats; Rats, Inbred Strains; Time Factors

Topics: Administration, Oral; Bacterial Infections; Denmark; Dysentery, Amebic; Humans; Hydroxyquinolines; Legislation, Drug; Nervous System Diseases

Topics: Bismuth; Cardiovascular Diseases; Diazepam; Drug Therapy; Endocrine System Diseases; Gastrointestinal Diseases; Glafenine; Hepatitis; Humans; Hydroxyquinolines; Hypersensitivity; Infections; Kidney Diseases; Metabolic Diseases; Neoplasms; Nervous System Diseases; Practolol; Respiratory Tract Diseases; Rheumatic Diseases

Topics: Diaper Rash; Eye Diseases; Humans; Hydroxyquinolines; Infant; Nervous System Diseases; Oxyquinoline

Topics: Blindness; Disasters; Drug Industry; Hydroxyquinolines; Japan; Legislation, Drug; Nervous System Diseases; Paralysis; Paraplegia; Vision Disorders

Topics: Animals; Chloroquinolinols; Dogs; Hydroxyquinolines; Nervous System Diseases; Time Factors