P. H. Wu

The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in the dog

Behavioral and pharmacological effects of oral administration ofl-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected byl-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested thatl-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects ofl-deprenyl on behavior and cognitive function.

deprenyl increases activities of Superoxide Dismutase (SOD) in striatum of dog brain

Seven beagle dogs were administered sucrose (control animals) or different doses of (-)deprenyl orally by means of capsules for 3 weeks. Activities of Cu Zn-SOD and Mn-SOD were determined in striatum and hippocampus in these animals. There was a significant dose-dependent increase in activities of total as well as in both types of SOD enzymes in striatum but not in hippocampus. The results suggest that this monoamine oxidase B inhibitor can increase antioxidant enzyme activities in striatum but not in hippocampus in the dog, thus showing brain region selectivity. These results are in accordance with previously published observations in rats.

Chronic ethanol inhibits rat hippocampal “stimulus-secretion” coupling mechanism for 5-hydroxytryptamine in vitro

Effects of ethanol on serotonergic neurotransmission were investigated in crude mitochondrial fraction (P2 fraction) from rat brain hippocampus and hypothalamus. The [14C]5-HT preloaded P2 fraction was exposed to 45 mM KCl to induce 5-hydroxytryptamine release in vitro. Ethanol in vitro did not produce any significant inhibition of [14C]5-HT release until its concentration was greater than 100 mM. The K+-evoked45Ca uptake of hippocampal P2 fraction was unaffected b6 100 mM. However, 200 mM ethanol inhibited approximately 63% of K+-evoked45Ca uptake. Chronic ethanol (10g/kg/day) for 6 days inhibited [14C]5-HT release from hippocampus whereas it did not affect [14C]5-HT release from hypothalamus. Results indicate that chronic ethanol treatment may decrease serotonergic neurotransmission in selective brain regions. The reduction in 5-hydroxytryptamine release was the result of inhibition in “stimulus-secretion” coupling mechanism.

Monoamine oxidase inhibition by L-deprenyl depends on both sex and route of administration in the rat

The monoamine oxidase B (MAO-B) inhibitorl-deprenyl, widely used to treat Parkinsons disease, has frequently been studied in animal models. We have examined the effects of several variables on activity levels of MAO-A and B in rat brain and liver following chronic (3 wks) treatment withl-deprenyl. Significant effects were observed for sex (females showed lower overall MAO-B activity in the liver), dose (MAO-A and B inhibition increased with dose, with females exhibiting greater sensitivity), route of administration (subcutaneous injection was more efficient than oral dosing), and dosing interval (MAO-B was significantly inhibited when dosing interval was increased to as long as 168 hours). Our results thus indicate that the effectiveness ofl-deprenyl in vivo is dependent on several factors and that these must be taken into account in studies involving the benefits or risks of this drug.