Clioquinol, neuropathy

Clioquinol Subacute myelo-optic neuropathy Approx 1930 51... 

Japan Clioquinol Drug used to treat travelers diarrhea found to cause neuropathy as many as 10 000 affected over two decades... 

The halogenated hydroxyquinolines include iodoquinol and clioquinol. Their mechanism of action is unknown. These agents can produce severe neurotoxicity and clioquinol is believed to have been responsible for the neurotoxic syndrome subacute myelo-optic neuropathy (SMON). 

A neuropathy caused by clioquinol (iodochlorohydroxyquin, chinoform) and enhanced by the formation of a clioquinol ferric chelate which initiates lipid peroxidation, leads to complete degeneration of retinal neuroblasts within a day. Vitamin E has a potent protective action against the effects of the chelate [75]. Peroxidative damage to DNA in rat brain, induced by methyl ethyl ketone peroxide, a potent initiator of lipid peroxidation, was inhibited by addition of vitamin E to the diet of rats [76]. 

There was a major epidemic of subacute myelo-optic neuropathy (SMON) in Japan during 1956-70. In 1970 a clinical observation led to case-control and cohort studies, which identified clioquinol as the culprit. A few cases were also reported elsewhere in the world, in Australia (2), Denmark (3), the Netherlands (4), Sweden (5-7), Switzerland (8), the UK (9-11), and the USA (12) some cases involved halogenated quinolines other than clioquinol. Prolonged use of diiodohydroxyquinoline in high doses has been associated with loss of vision and optic atrophy (SED-11, 594) (13). Halogenated quinolines were withdrawn in Japan and the epidemic abated (14). 

Arbiser JL, Kraeft SK, van Leeuwen R, Hurwitz SJ, Selig M, Dickersin GR, Flint A, Byers HR, Chen LB. Clioquinol-zinc chelate a candidate causative agent of subacute myelo-optic neuropathy. Mol Med 1998 4(10) 665-70. 

Halogenated hydroxyquinolines act on microorganisms in the intestinal tract and have been used for traveler s diarrhea. In Japan clioquinol (Vioform) has caused a subacute myelooptic neuropathy (SMON). The oral preparations have therefore been removed from the market in most countries. Clioquinol is still used topically and can cause contact dermatitis. A flare of contact dermatitis after oral intake has been reported (Leifer and Steiner 1951 Domar and Juhlin 1967 Ekelund and Moller 1969). 

Meade, T.W. (1975) Subacute myelo-optic neuropathy and clioquinol. An epidemiological case history for diagnosis. Brit. J. prev. soc. Med., 29,157. 

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