Lubazodone (developmental code names YM-992, YM-35995) is an experimental

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

which was under development by Yamanouchi for the treatment for

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...

in the late 1990s and early 2000s but was never marketed. It acts as a

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to increase ...

(K_i for = 21 nM) and 5-HT_2A receptor

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

(K_i = 86 nM), and hence has the profile of a

serotonin antagonist and reuptake inhibitor Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of seroto ...

(SARI). The drug has good

selectivity Selectivity may refer to: Psychology and behaviour * Choice, making a selection among options * Discrimination, the ability to recognize differences * Socioemotional selectivity theory, in social psychology Engineering * Selectivity (radio), a ...

against a range of other

monoamine receptor A monoamine receptor is a receptor for the monoamine neurotransmitters and/or trace amines, endogenous small-molecule signaling molecules with a monoamine structure. The monoamine receptors are almost all G protein-coupled receptors, with the sero ...

s, with its next highest affinities being for the α₁-adrenergic receptor (K_i = 200 nM) and the 5-HT_2C receptor (K_i = 680 nM). Lubazodone is structurally related to

trazodone Trazodone, sold under many brand names, is an antidepressant medication. It is used to treat major depressive disorder, anxiety disorders, and difficulties with sleep. The medication is taken orally. Common side-effects include dry mouth, fe ...

and

nefazodone Nefazodone, sold formerly under the brand names Serzone, Dutonin, and Nefadar among others, is an atypical antidepressant which was first marketed by Bristol-Myers Squibb (BMS) in 1994 but has since largely been discontinued. BMS withdrew it from ...

, but is a stronger serotonin reuptake inhibitor and weaker as a 5-HT_2A receptor antagonist in comparison to them and is more balanced in its actions as a SARI. It reached phase II

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s for depression, but development was discontinued in 2001 reportedly due to the "erosion of the market in the United States".

Synthesis

Thus reaction of 7-fluoro-4-indanol 61178-24-1(1) with (S)-glycidyl methanesulfonate
CID:12461090
(2) in the presence of base leads to the epoxypropyl ether
CID:139677486
(3). Treatment with aminoethyl sulfate 26-39-6(4) closes the morpholine ring giving Lubazodone (5).

References

External links

Lubazodone - AdisInsight
5-HT2A antagonists Alpha-1 blockers Antidepressants Indanes Morpholines Organofluorides Phenol ethers Serotonin reuptake inhibitors {{nervous-system-drug-stub