Melior Discovery drug abuse liability

Withdrawal / Dependence
The purpose of conducting the dependence liability study is to assess whether repeated or continuous administration of the test drug itself will produce neuroadaptive changes that result in physical dependence as indicated by the presence of a withdrawal syndrome (e.g., teeth chatter, yawns, shakes/tremors, abdominal writhes/gasps) upon cessation of the drug treatment (i.e., spontaneous withdrawal). If withdrawal syndrome is observed in animals, the likelihood of the test drug producing physical dependence is quite high which may lead to uncontrollable drug use in humans.  Dependence liability study is recommended if the mechanism of action of the test drug is uncertain, demonstrates novel mechanism of action or does not share mechanisms of action with known drugs of abuse.

Typically, pre-determined drug maintenance doses (low mg kg⁻¹ day⁻¹, moderate mg kg⁻¹ day⁻¹ and high mg kg⁻¹ day⁻¹) are administered to three groups of rats (implanted previously with telemetry devices to measure systolic and diastolic blood pressure and heart rate) via mini-osmotic pumps for 7-14 days to induce physical dependence. Animals will be allowed to undergo spontaneous withdrawal. During spontaneous withdrawal, changes in systolic and diastolic blood pressure and heart rate will be monitored continuously for one week and data gathered will compared to pre-drug levels (within group) and to vehicle-control levels (between group).

If you are interested in learning more about Withdrawl / Dependence, please contact models@meliordiscovery.com to start the conversation.