Table 1.
General characteristics of included IBs.
| IB | Mechanism of Action | FIH | Starting dose rationale | Completeness of reporting; PK results of in vivo pharmacology experiments reported | Animal model justification | Internal validity |
|---|---|---|---|---|---|---|
| 1 | Cannabinoid receptor antagonist | No | In vivo pharmacology and safety | Dog: yes; Mouse: no; Rat: partial | None | No |
| 2 | Cannabinoid receptor agonist | Yes | Safety | Dog: partial; Micro-pig: no; Mini-pig: no; Mouse: no; Rat: partial | None | No |
| 3 | Orexin receptor antagonist | Yes | In vivo pharmacology and safety | Dog: partial; Guinea pig: no; Rats: partial | None | No |
| 4 | Cannabinoid receptor agonist | Yes | In vivo pharmacology and safety | Dogs: partial; Mini-pig: no; Mouse: no; Rat: partial | None | No |
| 5 | Cannabinoid receptor antagonist | Yes | In vivo pharmacology and safety | Dog: partial; Guinea-pig: no; Mouse: no; Rabbit: yes; Rat: partial | Pharmacological | No |
| 6 | Dopamine antagonist | No | Safety | Dogs: partial; Ferret: no; Guinea pig: partial; Mini-pig: yes; Monkey: yes; Mouse: partial; Rat: partial | Pharmacological | No |
| 7 | GABA receptor modulator | No | In vivo pharmacology and safety | Dog: yes; Guinea-pig: partial; Monkey: no; Mouse: no; Rat: partial | Pharmacological | No |
| 8 | Alpha 7 nicotinic acetylcholine receptor partial agonist | No | In vivo pharmacology and safety | Dog: partial; Monkey: partial; Mouse: partial; Rabbit: yes; Rat: partial | None | No |
| 9 | GABA-receptor partial agonist | Yes | Safety | Dog: partial; Mouse: no; Rat: partial | Commonly used/ pharmacological | No |
| 10 | Neublastin (GFRα3) co-receptor selective ligand | No | In vivo pharmacology and safety | Monkey: partial; Mouse: no; Rat: partial | Phenotypic | No |
| 11 | Orexin antagonist | Yes | Safety | Dog; partial; Guinea pig: no; Rat: partial | None | No |
| 12 | Histamine receptor agonist | Yes | Safety | Cat: partial; Dog: partial; Monkey: yes; Mouse: partial; Rat: partial | None | No |
| 13 | Histamine receptor antagonist | No | In vivo pharmacology and safety | Dog: yes; Monkey: partial; Mouse: no; Rat: partial | None | No |
| 14 | GABA-receptor selective positive allosteric modulator | Yes | In vivo pharmacology and safety | Dog: partial; Rat: partial, Mouse: partial | None | No |
| 15 | Alpha 7 nicotinic acetylcholine receptor agonist | No | In vivo pharmacology and safety | Dog: partial; Mouse: partial; Rat: partial | None | No |
| 16 | Orexin antagonist | No | In vivo pharmacology and safety | Dog: partial; Guinea pig: partial; Mouse: partial; Monkey: yes; Rat: partial | None | No |
| 17 | Trace amine associated receptor (TAAR)1 partial agonist | No | In vivo pharmacology and safety | Monkey: partial; Mouse: no; Rat: partial | None | No |
| 18 | Orexin receptor antagonist | Yes | Safety | Dog: partial; Guinea pig: partial; Rat: partial | None | No |
| 19 | P2X7 channel antagonist | No | In vivo pharmacology and safety | Rat: partial; Dog: no, Guinea pig: partial, Monkey: yes | None | No |
| 20 | Muscarinic receptor partial agonist | Yes | Safety | Dog: partial; Monkey: yes; Rat: partial | None | No |
| 21 | Nicotinic acetylcholine (nAChR) inhibitor (prodrug) | No | Safety | Dog: partial; Ferret: no; Mouse: partial; Rat: partial | Commonly used | No |
| 22 | Orexin receptor antagonist | Yes | Safety | Dog: partial; Guinea pig: partial; Mouse: partial; Rat: partial | None | No |
| 23 | Beta-glucocerebrosidase (GCase) allosteric activator | Yes | In vivo pharmacology and safety | Dog: yes; Monkey: yes; Mouse: partial; Rat: yes | Biomarker | No |
| 24 | GABA positive allosteric modulator | Yes | In vivo pharmacology and safety | Minipig: yes; Monkey: yes; Mouse: partial; Rat: partial | Symptomatology | No |
| 25 | AMPA receptor positive allosteric modulator | No | In vivo pharmacology and safety | Monkey: partial; Rat: partial | None | No |