Contrave™ and Empatic™ Scientific Rationale
Contrave
Contrave is a fixed-dose combination of bupropion sustained-release (SR) and naltrexone SR. Orexigen developed its own proprietary SR version of naltrexone to improve drug tolerability.
Bupropion acts on the weight control circuit by stimulating the POMC neuron.
Naltrexone prevents inhibition of POMC neurons by blocking the action of β-endorphin.
Empatic
Empatic is a fixed-dose combination of bupropion SR and zonisamide SR. Orexigen developed its own proprietary SR version of zonisamide to improve drug tolerability.
Bupropion acts on the weight control circuit by stimulating the POMC neuron.
Zonisamide increases monoamines, which we hypothesize suppresses the NPY/AgRP neuron and further stimulates the POMC neurons.
Obesity as a Central Nervous System (CNS) Disorder Detail
The POMC neuron releases the hormone α-MSH, which binds to MC-4 receptors.
As α-MSH is produced, β-endorphin is also produced and feeds back to inhibit the POMC neurons, as part of the body’s normal compensatory mechanism.
NPY/AgRP acts in a manner opposite to α-MSH.
When α-MSH binds to MC-4, AgRP cannot bind (and vice versa).
Monoamines including dopamine, norepinephrine and serotonin affect POMC and NPY/AgRP neurons. Monoamines stimulate POMC, causing an increase in α-MSH release. Monoamines inhibit NPY/AgRP neurons, resulting in decreased secretion of AgRP.