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

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Non-GLP, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment, original source is not available.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

1978

Report date:

1978

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

other: emetic effects

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Twelve healthy volunteers were orally dosed with 0.25, 0.5, 1.0, 2, 3, 4, and 8 mg. The emetic effects of the substance were studied. Based on the obtained results further studies were performed with a maximum dose of 2 mg.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

248-383-5

EC Name:

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

Cas Number:

27277-00-5

Molecular formula:

C9H13N5O

IUPAC Name:

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

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 12
- Demographic information: average weight 70 kg.

Ethical approval:

not specified

Route of exposure:

oral

Reason of exposure:

intentional

Details on exposure:

12 healthy volunteers were orally exposed to the test substance. Doses of 0.25 (n=1), 0.5 (n=1), 1.0 (n=2), 2 (n=3), 3 (n=2), 4 (n=2), and 8 (n=1) mg were given in tablet form. Based on the obtained results further studies were performed with a maximum dose of 2 mg.

Examinations:

The emetic effects of the substance were studied and blood levels of two volunteers were measured.

Results and discussion

Clinical signs:

The volunteer given 8 mg vomited as did the one given 4 mg. Nausea was a marked effect reported by almost all of the volunteers. The substance was tolerated poorly at doses above 1 - 2 mg. Nausea, vomiting, dissiness, sweating and flushing were complained of. Further studies performed with a maximum dose of 2 mg. Of those who took 2 mg, approximately 10% vomited and 60% complained of nausea.

See any other information on results incl. tables for an overview of the emetic action.

Results of examinations:

It can be seen that when the blood levels of the test substance in the 2 volunteers given 4 mg are compared, the one that vomited absorbed the compound more quickly than the other. Blood concentrations of one volunteer were 0.081, 0.041, and 0.034 micrograms/mL 1, 2, and 3 hours after dosing 4 mg, respectively. The blood concentrations of the other volunteer were 0.045, 0.056, 0.044 micrograms/mL 1, 2, and 3 hours after dosing 4 mg, respectively.

Any other information on results incl. tables

Emetic action

Dose (mg/kg)	Nos. vomiting	% vomiting response	Total dose (mg)
0.015	0/2	0	1
0.03	4/37	11	2
0.06	1/2	50	4
0.11	1/1	100	8

Applicant's summary and conclusion

Conclusions:

It can be concluded that the test substance can initiate emesis in humans at a dose of approximately 0.03 - 0.11 mg/kg bw (2 - 8 mg).

Executive summary:

Twelve healthy volunteers were orally dosed with 0.25, 0.5, 1.0, 2, 3, 4, and 8 mg. Plasma concentrations of the two volunteers dosed with 4 mg were determined. The blood concentrations of one volunteer were 0.081, 0.041, and 0.034 µg/mL and concentrations of the other volunteer were 0.045, 0.056, 0.044 µg/mL 1, 2, and 3 hours after dosing, respectively. Based on the obtained results further studies were performed with a maximum dose of 2 mg. Of those who took 2 mg test substance (about 0.03 mg/kg) approximately 10% vomited and 60% complained of nausea. It can be concluded that the test substance can initiate emesis in humans at a dose of approximately 0.03 - 0.11 mg/kg bw (2 - 8 mg).