Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042571 (vertigo)
 7,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metrifonate (0,0-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate) is an organophosphorus compound where there are excellent possibilities to make studies in man. Metrifonate and its rearrangement product dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP) were studied in human blood from schistosomiasis patients treated with Bilarcil. A mass fragmentographic technique was employed. Deuterium labelled variants of the substances were used, both as internal standards and to compensate for DDVP formed during the workup procedure. The amount of DDVP in plasma was about 1% of the amount of metrifonate. In erythrocytes the corresponding amount of DDVP in percent of metrifonate was half or less. Both compounds reached peak levels within two hours and were detectable for at least eight hours. The results were compared to erythrocyte and plasma cholinesterase determinations. Levels of metrifonate and DDVP, together with cholinesterase activity, have also been studied in mouse brain, liver and kidney. It is proposed that metrifonate acts as a slow release formulation for DDVP. Clearance of metrifonate in man occurs primarily via DDVP. Mild vertigo subsiding in a few hours was the most common side-effect.
 ...
PMID:Quantitation of metrifonate and dichlorvos in blood and tissues by gas chromatography-mass spectrometry. 718 87

Mefloquine is a quinoline derivative antimalarial which demonstrates promise for the treatment of schistosomiasis. Traditionally employed in prophylaxis and treatment of chloroquine-resistant Plasmodium falciparum malaria, recent changes to the approved European and U.S. product labeling for mefloquine now warn of a risk of permanent and irreversible neurological sequelae including vertigo, loss of balance and symptoms of polyneuropathy. The newly described permanent nature of certain of these neurological effects challenges the conventional belief that they are due merely to the long half-life of mefloquine and its continued presence in the body, and raises new considerations for the rational use of the drug against parasitic disease. In this opinion, it is proposed that many of the reported lasting adverse neurological effects of mefloquine are consistent with the chronic sequelae of a well characterized but idiosyncratic central nervous system (CNS) toxicity syndrome (or toxidrome) common to certain historical antimalarial and antiparasitic quinolines and associated with a risk of permanent neuronal degeneration within specific CNS regions including the brainstem. Issues in the development and licensing of mefloquine are then considered in the context of historical awareness of the idiosyncratic CNS toxicity of related quinoline drugs. It is anticipated that the information presented in this opinion will aid in the future clinical recognition of the mefloquine toxidrome and its chronic sequelae, and in informing improved regulatory evaluation of mefloquine and related quinoline drugs as they are explored for expanded antiparasitic use and for other indications.
...
PMID:Idiosyncratic quinoline central nervous system toxicity: Historical insights into the chronic neurological sequelae of mefloquine. 2505 61