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Otsuka Pharmaceutical in Japan built OPC-14523 to hit two antidepressant-relevant targets in one molecule, sigma receptors and the 5-HT1A receptor, without directly blocking the serotonin transporter the way an SSRI does. In rodent screens it cut immobility in the forced swim test, increased dorsal raphe serotonergic neuron firing with repeated dosing, and reversed both scopolamine-induced and age-associated memory impairment, a combination antidepressant and pro-cognitive profile that made it a heavily cited pharmacology tool through the early 2000s. There is no public record of it reaching a pivotal human depression trial; Otsuka's psychiatric pipeline moved in other directions, and OPC-14523 stayed a preclinical proof-of-concept rather than becoming a marketed drug.
- reduced immobility in forced-swim antidepressant screens
- reversed scopolamine-induced memory impairment in rats
- reversed age-associated memory impairment in aged rodents
- increased dorsal raphe serotonergic neuron firing with chronic dosing
- OPC-14523 reversed memory impairment from both a drug challenge (scopolamine) and simple aging in separate rat studies, which drew interest from nootropic researchers as well as antidepressant researchers.
Mechanism
Combined sigma-1/sigma-2 and receptor (sigma1/2 IC50 ~47/56 nM, 5-HT1A IC50 ~2.3 nM) with weaker affinity at the transporter; chronic dosing increases the firing rate of serotonergic neurons in the dorsal raphe nucleus.
Safetyrisks and cautions, not medical advice
OPC-14523 has never been dosed in a human being, so there is no tolerability record to summarize and no safe dose to name. Its binding profile does flag one thing worth stating plainly: alongside the sigma and 5-HT1A activity it holds the serotonin transporter at nanomolar concentrations, which puts it in the same interaction territory as an SSRI and makes combination with other serotonergic drugs the obvious theoretical hazard. It showed no monoamine oxidase inhibition and no muscarinic affinity in screening. All of that is cell and rodent data.
History
Developed by Otsuka Pharmaceutical from the late 1990s through the mid-2000s; extensively characterized in rodent models of depression, anxiety, and memory impairment; no record of advancement into a registered human efficacy trial for depression.
Subjective profileweighing the evidence above
A thoroughly documented dual sigma/5-HT1A mechanism that proved out in animals but stayed in the lab.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Did OPC-14523 ever reach human trials?
There is no public record of it reaching a pivotal human depression trial; the available literature is preclinical, mostly in rats and mice.
Why combine sigma and 5-HT1A activity in one molecule?
The idea was to accelerate and strengthen an antidepressant signal without directly blocking the serotonin transporter, potentially sidestepping some SSRI-typical side effects.
Limitations of the evidence
- no human safety or tolerability data on record
- preclinical only, so real-world side effects in people are unknown