The pharmacology of selegiline ((-)deprenyl). New aspects.
Male rats were treated from the end of their 2nd year of life either with saline (1 ml/kg, s.c.) (n = 66) or with deprenyl (0.25 mg/kg, s.c.) (n = 66) three times a week until death. Whereas none of the two-year-old saline-treated rats displayed full scale sexual activity, this appeared in 64 out of 66 rats on deprenyl. The longest living rat in the saline-treated group lived 164 weeks. The average lifespan of the group was 147.05 +/- 0.56 weeks. The shortest living animal in the (-)deprenyl-treated group lived 171 weeks and the longest living rat died during the 226th week of its life. The average lifespan was 191.91 +/- 2.31 weeks. This is the first instance that a well-aimed medication prolonged lifespan of members of a species beyond their maximum age of death (182 weeks in the rat). A close relation between sexual activity and lifespan was detected. Male rats (n = 94) selected from an 8-month old population as sexually inactive ones were found to be miserable learners. This group was treated either with saline (1 ml/kg, s.c.) (n = 46) or with (-)deprenyl (0.25 mg/kg, s.c.) (n = 48) three times a week for 36 weeks. Their performance in the shuttle box during 5 consecutive days was tested before and after treatment. The total number of conditioned avoidance responses (CAR) which remained unchanged in the saline-treated group (6.53 +/- 1.41 before and 5.98 +/- 1.15 after treatment) increased from 5.57 +/- 0.65 to 20.73 +/- 1.39 (p less than 0.001) in the (-)deprenyl-treated group of rats. (-)Deprenyl-treatment (0.25-2 mg/kg, s.c., daily for 21 days) increased superoxide dismutase (SOD) activity in the striatum of CFY rats, whereas clorgyline-treatment (0.1-1 mg/kg) inhibited it.
Knoll
J
J
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D007858:Learning / Q000187:drug effects; D008136:Longevity / Q000187:drug effects; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D012642:Selegiline / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
D010627:Phenethylamines; D012642:Selegiline; D013482:Superoxide Dismutase