Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large number of reports have been devoted to the physiologic and toxic effects of methyl chloride, many of which are based on case histories involving occupational exposure. The detrimental actions of methyl chloride on the central and peripheral nervous systems are well established effects. It is a moderately severe narcotic and potentially severe nerve poison. Chronic intoxication is associated with damage to the central nervous system (CNS), kidneys, liver, bone marrow, cardiovascular system, respiratory system, and intestinal tract. The signs and symptoms range from the more severe medical dysfunctions such as cardiac irregularities, respiratory paralysis, nerve degeneration, and severe convulsions to the more subtle clinical observations such as CNS depression, nervousness and emotional instability, insomnia and anorexia, ataxia, blurred vision, light-headedness, nausea, dizziness, narcosis, and disorientation. The behavioral correlates of these and other neurotoxic effects of methyl chloride suggest that a gradual behavioral degradation occurs. Pharmacodynamic studies have shown the compound to be rapidly absorbed by the blood with most authors attributing the toxicity to an enzyme-catalyzed methylation reaction in the body. Despite the fact that several investigators have attempted to correlate such biological responses of methyl chloride with its toxicity, the present knowledge of the problem still lacks a detailed mechanism of action. Until such mechanisms are verified, adequate methods to assess subclinical neurological and behavioral changes must be effectively developed.
CRC Crit Rev Toxicol 1979 Nov
PMID:Behavioral, neurological, and toxic effects of methyl chloride: a review of the literature. 38 67

3,5-Dichloro-2,4-dimethoxy-6-(trichloromethyl)pyridine (penclomedine, NSC 338720, CRC 88-04) is an alpha-picoline derivative with anti-tumour activity in preclinical models. Penclomedine administration by 1-h intravenous infusion on 5 consecutive days was repeated 3 weekly in the absence of dose-limiting toxicity (DLT) or disease progression. Five dose levels were investigated (22.5-340 mg m(-2) day[-1]). Eight men and eight women were entered, median age 59 years (range 39-73 years), with good performance status (ECOG 0/1) in 11 patients. A total of 13 out of 16 patients had received previous chemotherapy. Common toxicity criteria grade (CTCg) II vomiting was recorded at all dose levels. Neurotoxicity (cerebellar ataxia and dizziness) was the DLT, CTCg III toxicity occurring in three out of three patients treated at 340 mg m(-2) day(-1). CTCg III dizziness was noted in one out of three patients at 250 mg m(-2) day(-1). Neurotoxicity developed during the 1-h infusion and persisted for a variable period (maximum 5 h) after infusion. Prophylactic antiemetic drugs appeared to reduce associated vomiting but did not prevent ataxia. No antiproliferative toxicities were noted and no anti-tumour responses were documented. Penclomedine pharmacokinetic studies confirmed preclinical evidence of extensive apparent distribution (93 l m[-2]) and rapid clearance (41 l h[-1] m[-2]). Purkinje cell loss has been identified in preclinical models after intraperitoneal administration (O'Reilly et al, 1996a) and further clinical development of penclomedine will focus on oral administration.
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PMID:Dose-limiting neurotoxicity in a phase I study of penclomedine (NSC 388720, CRC 88-04), a synthetic alpha-picoline derivative, administered intravenously. 951 62