2-amino-6-methyl-4-propyl-1,2,4-triazolo[1,5-a]pyrimidin-5(4H)-one

Neurotoxicity

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The test substance is a known emetic in humans (Bayliss, 1973) therefore tests in non-vomiting species are less relevant. These studies were all performed in rat and mice, which are non-vomiting species. It should be noted that the dosed test substance might be more available for absorption in non-vomiting species compared to vomiting species.

The test substance shows in experimental animals a variety of effects also shown at comparable doses by many of the drugs used in the treatment of mental disease. The profile of activities of the test substance is not, however, the same as any of the known clinically useful drugs. Some of these standard drugs, such as the benzdiazepines (e.g. chlordiazepoxide) and the barbiturates, protect mice from electroshock. The test substance does not, but it shares with these two types of drug the properties of decreasing both the motility of mice and the time that these animals balance on a stationary or rotating rod. This decrease of agility and motility is shown by such drugs as the phenothiazines (e.g. chlorpromazine) and the propiophenones (e.g. haloperidol). These two drugs decrease the temperature of mice which is a property shared by the test substance. Under the conditions chosen, these two types of drug decrease the amount of food eaten by starved mice; at relatively low doses the test substance has the same effect . The response of mice to intraperitoneal acetic acid (squirming movements) is decreased by the test substance which also increased the reaction time of the animals when placed on a hot plate. These effects could be due to an analgesic action. Like many drugs used as sedatives, the test substance increases the time required by mice to regain their righting reflexes after treatment with barbiturates. The tricyclic antidepressants (e.g. imipramine) antagonise the hypothermic action of reserpine on mice. They do not affect their temperature, agility, motility or food intake. The hypothermic action of reserpine on mice is antagonised by the test substance. This effect shown at relatively low doses is not due to inhibition of the enzyme monoamine oxidase. The antidepressant drugs of the imipramine type potentiate the action of adrenalin and other catecholamines on the nictitating membrane of the cat; the test substance does not. It is, therefore, unlikely that the increase of the temperature of reserpinised mice by the test substance is due to a potentiation of catecholamines as is thought to be the case with imipramine. In mice, the test substance slightly increases the toxicity of d-amphetamine.

 

Under the conditions chosen, the test substance alters the electro­corticogram of conscious rats in the same direction as d-amphetamine and in a different direction to imipramine. In contrast, the test substance has, in animals, many of the properties of the drugs which depress the central nervous system. These results also show that these actions are not identical in all respects with those of any of the major types of drug used in the treatment of mental disease.