TY - JOUR
T1 - Combined effects of methadone and quetiapine on respiratory rate, haemodynamic variables, and temperature in conscious rats
AU - Andersen, Freja Drost
AU - Steffensen, Simon Comerma
AU - Vistisen, Simon Tilma
AU - Pinilla, Estefano
AU - Pedersen, Tina Myhre
AU - Matchkov, Vladimir
AU - Simonsen, Ulf
AU - Andersen, Charlotte Uggerhøj
PY - 2023/9
Y1 - 2023/9
N2 - Fatal poisonings where both methadone and quetiapine are detected post-mortem occurs frequently in legal autopsy cases. It is unclear whether quetiapine increases the risk of fatal methadone poisoning or if it is merely detected due to widespread use. We hypothesized that methadone and quetiapine would have additive toxic effects on respiratory rate, blood pressure, and the QTc-interval. To investigate this hypothesis, we used telemetry implants for measurements of respiratory rate, haemodynamic variables, the velocity of blood pressure changes, temperature, and movement in conscious, freely moving male Wistar rats aged 12-13 weeks. The combined effects of three accumulative i.p. doses of methadone (2.5, 10, 15 mg/kg) and quetiapine (3, 10, 30 mg/kg) were compared to rats treated with the same doses of each drug alone, and a vehicle-treated group in a randomized investigator blinded study. No additive effects of quetiapine and methadone on respiratory rate, haemodynamic variables, or movement were observed. However, body temperature was significantly lower by approximately 1.5°C on average in the group treated with both methadone and quetiapine (15 + 30 mg/kg) compared to the other groups. This indicates a synergistic effect of quetiapine and methadone on thermoregulation, which may increase the risk of fatal poisoning. We suggest studying this finding further in human settings.
AB - Fatal poisonings where both methadone and quetiapine are detected post-mortem occurs frequently in legal autopsy cases. It is unclear whether quetiapine increases the risk of fatal methadone poisoning or if it is merely detected due to widespread use. We hypothesized that methadone and quetiapine would have additive toxic effects on respiratory rate, blood pressure, and the QTc-interval. To investigate this hypothesis, we used telemetry implants for measurements of respiratory rate, haemodynamic variables, the velocity of blood pressure changes, temperature, and movement in conscious, freely moving male Wistar rats aged 12-13 weeks. The combined effects of three accumulative i.p. doses of methadone (2.5, 10, 15 mg/kg) and quetiapine (3, 10, 30 mg/kg) were compared to rats treated with the same doses of each drug alone, and a vehicle-treated group in a randomized investigator blinded study. No additive effects of quetiapine and methadone on respiratory rate, haemodynamic variables, or movement were observed. However, body temperature was significantly lower by approximately 1.5°C on average in the group treated with both methadone and quetiapine (15 + 30 mg/kg) compared to the other groups. This indicates a synergistic effect of quetiapine and methadone on thermoregulation, which may increase the risk of fatal poisoning. We suggest studying this finding further in human settings.
KW - Animals
KW - Hemodynamics
KW - Humans
KW - Male
KW - Methadone/pharmacology
KW - Quetiapine Fumarate/pharmacology
KW - Rats
KW - Rats, Wistar
KW - Respiratory Rate
KW - Temperature
UR - http://www.scopus.com/inward/record.url?scp=85168525791&partnerID=8YFLogxK
U2 - 10.1111/adb.13320
DO - 10.1111/adb.13320
M3 - Journal article
C2 - 37644895
SN - 1369-1600
VL - 28
JO - Addiction Biology
JF - Addiction Biology
IS - 9
M1 - e13320
ER -