Table II.
Effect of different agonistic and antagonistic treatments targeting GPCRs in patients with schizophrenia.
| Drug | Typical GPCR-associated signaling | Atypical GPCR-associated signaling |
|---|---|---|
| Aripiprazole | Dopamine Antagonist (√√√) D2 Gi ↓cAMP ↓Ca2+ ↓IK+; (√√) D3 Gi ↓ cAMP; (√) D4Gi ↓cAMP ↓Ca2+ ↓IK+ |
Serotonin Antagonist (√√√) 5HT1a Gs cAMP; (√√√) 5HT2a Ca2+ PLC; (Ö) 5HT2c Ca2+ PLC; (√) 5HT7 Gs↑ cAMP Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+ Histamine Antagonist (√) H1 Gq IP3/Ca2+ |
| Azepine | Dopamine Antagonist (ÖÖÖ) D2 Gi ↓cAMP ↓Ca2+ ↓IK+; (√) D3 Gi −cAMP |
Serotonin Antagonist (√√√√) 5HT Ca2+ 2a PLC; (√√) 5HT1a Gs ↑cAMP; (√√) 5HT1b Gi ↓cAMP; (√√) 5HT2c Ca2+ PLC; (√) 5HT6 Gs ↑cAMP; (√) 5HT7 Gs ↑Camp |
| Chlorpromazine | Dopamine Antagonist (√√√) D1 Gs ↑cAMP; (√√) D5 Gs ↑ cAMP; (Ö) D2 Gi ↓cAMP ↓Ca2+ −IK+; (√) D3 Gi ↓cAMP |
Serotonin Antagonist (√√√) 5HT1a Gs ↑cAMP; (√√√) 5HT2a Ca2+ PLC Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+; (√√) a2 Gi ↓cAMP Histamine Antagonist (√) H1 Gq IP3/Ca2+ Muscarinic Antagonist (√) M1 Gq IP3/Ca2+; (√) M2 Gi ↓cAMP −IK+ |
| Clozapine | Dopamine Antagonist (√√√) D1 Gs cAMP; (√√) D4 Gi ↑ cAMP ;(Ö) D2 Gi ↓ cAMP ↓ Ca2+ ↓IK+; (√) D3 Gi ↓ cAMP |
Serotonin Antagonist (√√√) 5HT2a Ca2+ PLC Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+ Muscarinic Antagonist (√√) M1 Gq IP3/Ca2+; (√) M2 Gi ↓cAMP −IK+; (√) M3 Gq IP3/Ca2+ Muscarinic Agonist (√) M4 Gi ↓cAMP ↓IK+ |
| Fluphenazine | Dopamine Antagonist (√√√) D2 Gi ↓cAMP ↓Ca2+ ↓IK+ |
Muscarinic Antagonist (√√) M1 Gq IP3/Ca2+ Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+ Histamine Antagonist (√) H1 Gq IP3/Ca2+ |
| Haloperidol | Dopamine Antagonist (√√√) D1 Gs ↑ cAMP; (√√) D2 Gi ↓cAMP −Ca2+ ↓IK+ | Muscarinic Antagonist (√) M1 Gq IP3/Ca2+ Adrenergic Antagonist (√) a1 Gq IP3/Ca2+ |
| Olanzapine | Dopamine Antagonist (√√√) D1 Gs ↑ cAMP; (√√) D5 Gs ↑ cAMP; (√√) D2 Gi ↓cAMP −Ca2+ ↓IK+; (√) D3 Gi ↓cAMP |
Serotonin Antagonist (√√√) 5HT Ca2+ 2a PLC; (√√√) 5HT2c Ca2+ PLC Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+ Muscarinic Antagonist (√√) M1 Gq IP3/Ca2+; (√) M2 Gi ↓ cAMP ↓IK+; (√) M3 Gq IP3/Ca2+; (√) M4 Gi ↓cAMP −IK+; (√) M5 Gq IP3/Ca2+ Histamine Antagonist (√) H1 Gq IP3/Ca2+ |
| Quetiapine | Dopamine Antagonist (√√) D1 Gs ↑ cAMP; (√√) D2 Gi ↓cAMP ↓Ca2+ ↓IK+ |
Serotonin Antagonist (√√√) 5HT2 Ca2+ PLC; (√√√) 5HT1 Gi ↓cAMP −IK+ Histamine Antagonist (√) H1 Gq IP3/Ca2+ Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+; (√) a2 Gi ↓ cAMP |
| Perphenazine | Dopamine Antagonist (√√) D2 Gi ↓cAMP ↓Ca2+ ↓IK+ |
Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+ |
| Risperidone | Dopamine Antagonist (√√) D2 Gi ↓cAMP ↓Ca2+ −IK+; (√) D3 Gi ↓ cAMP |
Serotonin Antagonist (√√√) 5HT2 Ca2+ PLC Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+ Histamine Antagonist (√) H1 Gq IP3/Ca2+ Muscarinic Antagonist (√√) M1 Gq IP3/Ca2+; (√√) M2 Gi ↓cAMP −IK+ |
| Thioridazine | Dopamine Antagonist (√√) D2 Gi
−cAMP ↓Ca2+ ↓IK+ |
Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+ |
| Trifluoperazine | Dopamine Antagonist (√√) D2 Gi ↓cAMP ↓Ca2+ ↓IK+ |
Adrenergic Antagonist (√√) a1 Gq IP3/Ca2+ |
| Ziprasidone | Dopamine Antagonist (√√) D2 Gi ↓cAMP ↓Ca2+ ↓IK+ ; (√) D3 Gi ↓cAMP |
Serotonin Antagonist (√√√) 5HT Ca2+ 2a PLC; (√√) 5HT Ca2+ 2c PLC; (√√) 5HT1d Gi ↓cAMP ↓Ca2+ ↓IK+ Adrenergic Antagonist (√) a1 Gq IP3/Ca2+ Histamine Antagonist (√) H1 Gq IP3/Ca2+ |
(√√√) High effect; (√√) Moderate effect; (√) Mild effect; ↓ decreased effect; ↑ increased effect. The information of this table was taken from (2,292,303). GPCR, G protein-coupled receptor; IK, potassium current; 5-HT, serotonin; PLC, phospholipase C; IP3, inositol 1,4,5-trisphosphate; Gi, G inhibitory; Gs, G stimulatory.