Organometal-induced antinociception: a time- and dose-response comparison of triethyl and trimethyl lead and tin.
Recent reports have demonstrated that organolead and -tin compounds can alter behavioral reactivity to noxious stimuli. To further define the dose response and temporal characteristics of these neurobehavioral effects, male Fischer 344 rats were injected sc with either one-fourth, one-half, or three-fourths the acute LD50 of triethyl lead (TEL), triethyl tin (TET), trimethyl lead (TML), trimethyl tin (TMT), or distilled water and tested on a 57.5 degrees C hot plate 1, 7, 14, 21, and 28 days after dosing. All four organometals altered hot plate latencies, but the magnitude and time course of these effects differed among the compounds. TEL produced a dose-related increase in latencies which was maximal 1 and 7 days postdosing and had dissipated by 28 days. In contrast, the group administered TML (3/4 LD50) exhibited a late developing antinocioception which became evident 14 days after dosing and persisted throughout the period of testing. The intermediate dose of TMT (1/2 LD50) also produced a delayed increase in response times which was observed 21 and 28 days post-treatment. The 3/4 LD50 dose of TMT produced increased hot plate latencies on all post-treatment test days except Day 14. TET (1/2 LD50) produced increased hot plate latencies 1, 7, 14, and 21 days postdosing and also induced a reversible ataxia and akinesia. Higher doses of TET proved lethal to 80% of the animals and lower doses failed to alter response times in the hot plate. These data demonstrate that trialkyl lead and tin compounds can produce time- and dose-related increases in hot plate latencies.
D000818:Animals; D002493:Central Nervous System Diseases / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000633:toxicity; D007855:Lead Poisoning / Q000503:physiopathology*; D007928:Lethal Dose 50; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity*; D009947:Organotin Compounds / Q000633:toxicity*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects; D013756:Tetraethyl Lead / Q000031:analogs & derivatives / Q000633:toxicity; D013997:Time Factors; D014267:Triethyltin Compounds / Q000633:toxicity; D014298:Trimethyltin Compounds / Q000633:toxicity
D009942:Organometallic Compounds; D009947:Organotin Compounds; D014267:Triethyltin Compounds; D014298:Trimethyltin Compounds; D013756:Tetraethyl Lead; D007854:Lead; C031575:triethyltin; C010360:triethyllead; C039474:trimethyllead