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Biomedical subjects

J Knoll

Publications and source records attributed to J Knoll.

At least 55 records · Page 3Linked to original sources

Chromatographic studies on the binding, action and metabolism of (-)-deprenyl.

Serum binding, the effect on striatal dopamine release and the metabolism of (-)-deprenyl [N-methyl-N-propargyl(2-phenyl-1-methyl)ethylammonium chloride], TZ-650 [N-methyl-N-propargyl(2-phenyl)ethylammonium chloride] and J-508 [N-methyl-N-propargyl(indanyl)ammonium chloride] were investigated using various chromatographic methods. A strong interaction between (-)-deprenyl and macroglobulins was found. Deprenyl enhanced the dopamine release from striatal slices of the rat brain and also inhibited the dopamine-DOPAC conversion. Deprenyl analogues showed either smaller or no effect. Hydroxylation of (-)-deprenyl takes place in the para position, in addition to the usual oxidative N-dealkylations, which are known from various metabolic studies on N-substituted phenylalkylamines.

Animals↗

Striatal dopamine, sexual activity and lifespan. Longevity of rats treated with (-)deprenyl.

The influence of longterm deprenyl treatment on the sexual performance and lifespan of male rats was studied. One hundred and thirty two 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 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 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.

Aging↗

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.

Animals↗

The effect of some anti-ulcer agents on the early vascular injury of gastric mucosa induced by ethanol in rats.

The effect of some gastroprotective agents cysteamine, sodium salicylate, atropine, cimetidine, and pyrido-pyrimidine derivatives, rimazolium, Ch-127 and a mast cell stabilizer, BMY-26517-31 was studied on the enhanced vascular permeability of gastric mucosa induced by 100% ethanol, on the enhanced vascular permeability of peritoneal blood vessels due to 0.3% acetic acid and on carrageenin edema test. We found that cysteamine, sodium salicylate, rimazolium and BMY-26517-31 inhibited the alcohol-induced enhanced vascular permeability. They also decreased the carrageenin-induced edema and--with the exception of BMY-26517-31--the acetic-acid-induced enhanced vascular permeability of the peritoneal vessels. These results suggest that similar events are present in the early phase of acute inflammation and chemically induced mucosal lesions. Consequently, antiinflammatory activity might play role in the protective mechanism of some anti-ulcer agents.

Acetates↗

The striatal dopamine dependency of life span in male rats. Longevity study with (-)deprenyl.

Long-term experiments on male rats revealed that better performers in the mating test are better learners in the shuttle box and the more active animals live significantly longer than their less active peers. It was established by the aid of (-)deprenyl, a highly specific chemical tool, which increases superoxide dismutase activity in the striatum, facilitates the activity of the nigrostriatal dopaminergic neurons with utmost selectivity, and protects these neurons from their age-related decay, that the efficiency of a male rat in behavioral tests, as well as the duration of its life are striatal dopamine dependent functions. As a measure of striatal function, sexual activity was tested once a week in a group of male rats (n = 132) from the 24th month of their life. Because of the age-related decay of this function none of the 2-year-old animals displayed full scale sexual activity. By dividing the group equally the rats were treated with saline (1 ml/kg, s.c.) and deprenyl (0.25 mg/kg, s.c.), respectively, three times a week. In the saline-treated group (n = 66) the last signs of sexual activity vanished to the 33rd week of treatment. (-)Deprenyl treatment restored full scale sexual activity in 64 out of 66 rats. 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 197.98 +/- 2.36 weeks, i.e. higher than the estimated maximum age of death in the rat (182 weeks). This is the first instance that by the aid of a well-aimed medication members of a species lived beyond the known lifespan maximum.

Aging↗