A Study on the Neurotoxicity of Broxyquinoline and Brobenzoxaldine Combination in Therapeutic Doses

Abstract

1 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).

2 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.

3 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 parasthesiae 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<0.001) increase in the stimulus strength for distal ulnar stimulation and a significant (P<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. 4 Literature on the neurotoxicity of the halogenated hydroxyquinolines is reviewed.

5 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.

Get full access to this article

View all access options for this article.

References

Baumgartner, G. , Gawel, M.J. , Kaeser, H.E. , Pallis, C.A. , Rose, F.C. , Schaum-Burg, H.H. , Thomas, P.K. & Wadia, N.H. (1979). Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan. J. Neurol. Neurosurg. Psychiatry, 42, 1073-1083.

Braddom, R.L. & Schuckmann, H. (1980). Motor conduction. In Practical Electromyography, ed. E. W. Johnson , pp. 34-36/42-44. Baltimore: William & Wilkins Co.

Hess, R. , Keberle, H. , Koella, W.P. , Schmid, K. & Gelzer, J. (1972). Clioquinol: absence of neurotoxicity in laboratory animals. Lancet, ii, 424.

Igata, A. , Hasebe, M. & Tsuji, T. (1970). On the green pigment found in SMON patients: two cases excreting greenish urine. Nippon Iji Shinpo (Japanese Journal of Medicine), 2421, 25-28 (in Japanese).

Imanari, T. & Tamura, Z. (1970). Detection of chinoform from green fur on the tongue of SMON patients. Igaku no Ayumi (Progress in Medicine) , 75, 547-548 (in Japanese).

Inoue, Y.K. (1971). The aetiology of SMON. Lancet , ii, 869.

Inoue, Y.K. (1975). The SMON virus theory. Lancet , ii. 984.

Inoue, Y.K. & Nishibe, Y. (1982). SMON and MS. Lancet, ii, 716.

Meade, T.W. (1975). Subacute myelo-optic neuropathy and clioquinol. An epidemiological case history for diagnosis. Br. J. Prevent. Soc. Med., 29, 157-169.

10.

Oakley, G.P. , JR (1973). The neurotoxicity of the halogenated hydroxyquinolines - a commentary. J. Am. Med. Assoc., 225, 395-397.

11.

Rollo, I.M. (1980). Drugs used in the chemotherapy of amebiasis. In The Pharmacological Basis of Therapeutics, 6th edn, eds L. S. Goodman & A. Gilman , pp. 1064-1065. New York: Macmillan.

12.

Shimada, Y. & Kosaka, K. (1973). New cases of SMON in Japan. Lancet , i, 268.

13.

Shimada, Y. & Tsuji, T. (1971). Halogenated oxyquinoline derivatives and neurological syndromes. Lancet, ii, 41.

14.

Steinitz, H. (1971). Halogenated oxyquinoline derivatives and neurological syndromes. Lancet, ii, 43.

15.

Strandvik, B. & Zetrerström, R. (1968). Amaurosis after broxyquinoline . Lancet, i, 922.

16.

Takasu, T. , Igata, A. & Toyokura, Y. (1970). On the green tongue observed in SMON patients . Igaku no Ayumi (Progress in Medicine), 72, 539 (in Japanese).

17.

Tateishi, J. , Kuroda, S. , Saito, A. & Otsuki, S. (1971). Myelo-optic neuropathy induced by clioquinol in animals. Lancet, ii, 1263.

18.

Tateishi, J. , Kuroda, S. , Saito, A. & Otsuki, S. (1972). Strain differences in dogs for neurotoxicity of clioquinol. Lancet, i, 1289.

19.

Tsubaki, T. , Honma, Y. & Hoshi, M. (1971). Neurological syndrome associated with clioquinol . Lancet, i, 696-697.

20.

Tsubaki, T. , Toyokura, Y. & Tsukagoshi, H. (1965). Subacute myelo-optico-neuropathy following abdominal symptoms: a clinical and pathological study. Nippon Iji Shinpo (Japanese Journal of Medicine), 4, 181-184 (in Japanese).

21.

Yoshioka, M. & Tamura, Z. (1970). On the nature of the green pigment found in SMON patients. Igaku no Ayumi (Progress in Medicine), 75, 320-322 (in Japanese).