Preferential distribution of alpha-hexachlorocyclohexane into cerebral white matter.
1. Whole-body autoradiographic evidence that alpha-1,2,3,4,5,6-hexachlorocyclohexane (alpha-HCH), a racemic compound with anticonvulsant and tremorogenic activities, accumulates in cerebral white over grey matter was confirmed in rats using unlabelled compound and g.l.c. determination in tissue samples. 2. Accumulation in, and retention by, cerebral white matter after a small intravenous dose was in marked excess of what may be accounted for by solvation and was due solely to the (+)-enantiomer. 3. Similar behaviour was exhibited by the (3,6/4,5)-isomers of 1,3,4,5,6-pentachlorocyclohex-1-ene (PCCH) and 1,2,3,4,5,6-hexachlorocyclohex-1-ene (HCCH) but not by other isomers of HCH, HCCH and PCCH suggesting that stereoselective binding to, presumably, some constituent of myelin might depend on the presence of a vicinal pair of (semi)-axially oriented carbon-chlorine bonds. 4. Evidence is presented which indicates that the anti-convulsant and tremorogenic effects of alpha-HCH are unlikely to be related to this property.
Portig
J
J
Institut für Toxikologie und Pharmakologie, Philipps-Universität, Marburg, F.R. Germany.
Stein
K
K
Vohland
H W
HW
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D001556:Hexachlorocyclohexane / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014202:Tremor / Q000139:chemically induced
D000927:Anticonvulsants; C040534:alpha-hexachlorocyclohexane; D001556:Hexachlorocyclohexane