CI-966
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| Routes of administration | Oral |
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CI-966 (developmental code name) is a
neuroprotective therapeutic but was discontinued during clinical development due to the incidence of severe adverse effects at higher doses and hence was never marketed.[2]
In a
glutamate at the NMDA receptor",[8][9] and the psychiatric effects of CI-966 were also described as resembling those seen in patients with mania in addition to schizophrenia.[4] These research findings were responsible for the discontinuation of the clinical development of CI-966.[2][5][7] In addition, on the basis of these findings, the drug has been characterized as a hallucinogen similarly to the potent GABAA receptor full agonist muscimol (a constituent of the hallucinogenic Amanita muscaria (fly agaric) mushrooms).[10]
In contrast to CI-966, the marketed selective GAT-1 blocker (and
GABA transaminase (GABA-T) inhibitor (and hence also an indirect and non-selective GABA receptor agonist) vigabatrin has also been associated with acute psychotic episodes, hallucinations, and other psychiatric adverse reactions, albeit less commonly.[12][13][14]
See also
References
- ISBN 978-3-0348-8990-2.
- ^ ISBN 978-1-59259-466-5.
- S2CID 39073036.
- ^ S2CID 84577983.
- ^ ISBN 978-1-118-35446-9.
- ^ S2CID 30717285.
- ^ PMID 10637362.
- ISBN 978-0-203-29938-8.
- ISBN 9780080450445.
- S2CID 143868762.
- PMID 10903390.
- S2CID 26494867.
- PMID 10534259.
- S2CID 40041098.
Further reading
- Borden LA, Murali Dhar TG, Smith KE, Weinshank RL, Branchek TA, Gluchowski C (October 1994). "Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1". European Journal of Pharmacology. 269 (2): 219–224. PMID 7851497.
- Phillis JW (September 1995). "CI-966, a GABA uptake inhibitor, antagonizes ischemia-induced neuronal degeneration in the gerbil". General Pharmacology. 26 (5): 1061–1064. PMID 7557251.
- Sedman AJ, Gilmet GP, Sayed AJ, Posvar EL (1990). "Initial human safety and tolerance study of a GABA uptake inhibitor, Cl-966: Potential role of GABA as a mediator in the pathogenesis of schizophrenia and mania". Drug Development Research. 21 (3): 235–242. S2CID 84577983.