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| Clinical data | |
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| Other names | CVL-865; PF-06372865; PF-6372865 |
| Routes of administration | By mouth |
| Drug class | GABAA receptor positive allosteric modulator |
| Pharmacokinetic data | |
| Metabolism | CYP3A4[1] |
| Eliminationhalf-life | 11 hours[1] |
| Identifiers | |
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| CAS Number | |
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| IUPHAR/BPS | |
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| ChEMBL | |
| Chemical and physical data | |
| Formula | C22H21FN4O3S |
| Molar mass | 440.49 g·mol−1 |
| 3D model (JSmol) | |
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Darigabat (developmental code namesCVL-865,PF-06372865,PF-6372865) is aGABAergic medication which is under development for the treatment ofphotosensitive epilepsy,focal onset seizures,panic disorder, and otheranxiety disorders.[2][3] It was also under development for the treatment ofgeneralized anxiety disorder andchronic lower back pain, but development for these indications was discontinued.[2][3][4] It is taken viaoral administration.[2]
Darigabat acts as aGABAA receptor positive allosteric modulator[2][3][5] It is specifically apositive allosteric modulator thatselectively targetsα2,α3, andα5 subunit-containingGABAA receptors, with minimalfunctional activity atα1 subunit-containing GABAA receptors.[3][5] A dose of darigabat that achieved more than 80% receptor occupancy showed nosomnolence withdose titration, whereasbenzodiazepines, which are non-selective GABAA receptor positive allosteric modulators, achieve only 10 to 15% receptor occupancy whilst producing significant or severe somnolence.[3][5] It is theorized that α1 subunit-containing GABAA receptors preferentially mediatesedation,amnesia, andataxia, whereas α2 and α3 subunit-containing GABAA receptors mediateanxiolysis.[3][5] However, this model has also been questioned.[4] α1 subunit-containing GABAA receptors are said to be completely unaffected by darigabat.[6] Theelimination half-life of darigabat is 11 hours and it ismetabolized mainly byCYP3A4.[1]
In clinical trials conducted thus far,side effects of darigabat have includeddizziness,fatigue,headache, mild-to-moderatesomnolence,bradyphrenia (slowness of thought), modestmemory impairment, mildcognitive impairment,balance impairment, and feeling abnormal.[3][6] It has been described aswell-tolerated.[3][4]
Darigabat was originated byPfizer and is under development byCerevel Therapeutics andPfizer.[2] As of January 2023, it is inphase 2clinical trials for epilepsy and seizures,phase 1 trials for panic disorder, andpreclinical development for anxiety disorders.[2][3] Development for back pain was discontinued due to lack of effectiveness in a phase 2 trial, while development for generalized anxiety disorder was discontinued due to business reasons as well as lack of effectiveness in a phase 2 trial.[3][4][2]