Molecular and neurocircuitry targets for medications development to reverse hyperkatifeia of the withdrawal/negative affect stage for OUD and AUD
| Target | Manipulation | Opioids | Alcohol |
|---|---|---|---|
| Within-system | |||
| Dopamine | Dopamine receptor partial agonists | ✓ | ✓ |
| Opioid peptides | G protein modulators | ✓ | — |
| CREB | ✓ | — | |
| cAMP/PKA modulators | — | ✓ | |
| CREB | — | ✓ | |
| GABA/glutamate | GABA subunit receptor agonists | ✓ | ✓ |
| Glutamate receptor antagonists | ✓ | ✓ | |
| Between-system | |||
| CRF | CRF1 receptor antagonists | ✓ | ✓ |
| Dynorphin | κ-Opioid receptor antagonists | ✓ | ✓ |
| Vasopressin | V1b receptor antagonists | ✓ | ✓ |
| Norepinephrine | α1-Adrenergic receptor antagonists | ✓ | ✓ |
| α2-Adrenergic receptor agonists | ✓ | ✓ | |
| β-Adrenergic receptor antagonists | ✓ | ✓ | |
| Hypocretin | Hcrt-1 receptor antagonists | ✓ | ✓ |
| Hcrt-2 receptor antagonists | ✓ | ✓ | |
| Neuroimmune system | Neuroimmune modulators | ||
| Tumor necrosis factor | ✓ | ✓ | |
| Phosphodiesterase inhibitors | — | ✓ | |
| Antistress modulators | |||
| NPY | Y1 receptor agonists | ✓ | ✓ |
| Y2 receptor antagonists | ✓ | ✓ | |
| Nociceptin | Nociceptin receptor agonists | ✓ | ✓ |
| Endocannabinoids | FAAH inhibitors | ✓ | ✓ |
| MAGL inhibitors | ✓ | ✓ | |
| Oxytocin | Oxytocin receptor agonists | ✓ | ✓ |
| Hyperalgesia/pain | |||
| Glutamate | NMDA receptor antagonists | ✓ | ✓ |
| CRF | CRF1 receptor antagonists | ✓ | ✓ |
| Dynorphin | κ-Opioid receptor antagonists | ✓ | — |
| Melanocortin | Melanocortin receptor 4 antagonists | ✓ | ✓ |
| PKC | PKCε inhibitor | — | ✓ |
| PKCγ inhibitor | ✓ | — | |
| Serotonin | 5-HT2A receptor antagonist | — | ✓ |
PKA, protein kinase A; —, no data available; 5-HT2A, 5-hydroxytryptamine-2A.