Zalospirone

Last updated
Zalospirone
Zalospirone.svg
Clinical data
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Pharmacokinetic data
Elimination half-life 1-4 hours
Identifiers
  • (3aα,4α,4aβ,6aβ,7α,7aα)-Hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-4,7-etheno-1H-cyclobut[f]isoindole-1,3(2H)-dione
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C24H29N5O2
Molar mass 419.529 g·mol−1
3D model (JSmol)
  • O=C1N(C(=O)[C@@H]4[C@H]1[C@@H]2\C=C/[C@H]4[C@H]3\C=C/[C@@H]23)CCCCN6CCN(c5ncccn5)CC6
  • InChI=1S/C24H29N5O2/c30-22-20-18-6-7-19(17-5-4-16(17)18)21(20)23(31)29(22)11-2-1-10-27-12-14-28(15-13-27)24-25-8-3-9-26-24/h3-9,16-21H,1-2,10-15H2/t16-,17+,18-,19+,20-,21+
  • Key:AERLHOTUXIJQFV-RCPZPFRWSA-N
   (verify)

Zalospirone (WY-47,846) is a selective 5-HT1A partial agonist of the azapirone chemical class. [1] [2] It was found to be effective in the treatment of anxiety and depression in clinical trials, but a high proportion of subjects dropped out due to side effects and development was subsequently never completed. [3]

See also

Related Research Articles

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5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

<span class="mw-page-title-main">Azapirone</span> Drug class of psycotropic drugs

Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).

<span class="mw-page-title-main">Buspirone</span> Medication used to treat anxiety disorders

Buspirone, sold under the brand name Buspar, among others, is an anxiolytic, a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder (GAD). It is a serotonin 5-HT1A receptor partial agonist, increasing action at serotonin receptors in the brain. It is taken orally, and takes two to six weeks to be fully effective.

<span class="mw-page-title-main">Pindolol</span> Chemical compound

Pindolol, sold under the brand name Visken among others, is a nonselective beta blocker which is used in the treatment of hypertension. It is also an antagonist of the serotonin 5-HT1A receptor, preferentially blocking inhibitory 5-HT1A autoreceptors, and has been researched as an add-on therapy to various antidepressants, such as clomipramine and the selective serotonin reuptake inhibitors (SSRIs), in the treatment of depression and obsessive-compulsive disorder.

<span class="mw-page-title-main">Ipsapirone</span> Antidepressant and anxiolytic drug

Ipsapirone is a selective 5-HT1A receptor partial agonist of the piperazine and azapirone chemical classes. It has antidepressant and anxiolytic effects. Ipsapirone was studied in several placebo-controlled trials for depression and continues to be used in research.

<span class="mw-page-title-main">Tandospirone</span> Anxiolytic and antidepressant medication

Tandospirone, sold under the brand name Sediel, is an anxiolytic and antidepressant medication used in Japan and China, where it is marketed by Dainippon Sumitomo Pharma. It is a member of the azapirone class of drugs and is closely related to other azapirones like buspirone and gepirone.

5-HT<sub>1A</sub> receptor Serotonin receptor protein distributed in the cerebrum and raphe nucleus

The serotonin 1A receptor is a subtype of serotonin receptors, or 5-HT receptors, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.

<span class="mw-page-title-main">8-OH-DPAT</span> Chemical compound

8-OH-DPAT is a research chemical of the aminotetralin chemical class which was developed in the 1980s and has been widely used to study the function of the 5-HT1A receptor. It was one of the first major 5-HT1A receptor full agonists to have been discovered.

<span class="mw-page-title-main">WAY-100635</span> Chemical compound

WAY-100635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the D4 receptor. It is sometimes referred to as a silent antagonist at the former receptor. It is closely related to WAY-100135.

<span class="mw-page-title-main">Flesinoxan</span> Chemical compound

Flesinoxan (DU-29,373) is a potent and selective 5-HT1A receptor partial/near-full agonist of the phenylpiperazine class. Originally developed as a potential antihypertensive drug, flesinoxan was later found to possess antidepressant and anxiolytic effects in animal tests. As a result, it was investigated in several small human pilot studies for the treatment of major depressive disorder, and was found to have robust effectiveness and very good tolerability. However, due to "management decisions", the development of flesinoxan was stopped and it was not pursued any further.

<span class="mw-page-title-main">Binospirone</span> Anxiolytic drug

Binospirone (MDL-73,005-EF) is a drug which acts as a partial agonist at 5-HT1A somatodendritic autoreceptors but as an antagonist at postsynaptic 5-HT1A receptors. It has anxiolytic effects.

<span class="mw-page-title-main">Perospirone</span> Atypical antipsychotic medication

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.

Naluzotan is a serotonergic drug of the phenylpiperazine class that was under investigation by EPIX Pharmaceuticals Inc for the treatment of generalized anxiety disorder and major depressive disorder. It acts as a selective and potent 5-HT1A receptor partial agonist, readily stimulating prolactin responses, though it has also been found to bind to and activate the σ receptor. Naluzotan was well tolerated in clinical trials, with more patients in the control group dropping out due to adverse effects than in the active group in one study. The most frequently reported side effect was headache in 15% of patients. In addition, naluzotan demonstrated significant antidepressant and anxiolytic effects as per the HAM-D and MADRS and the HAM-A, respectively, in some trials, but in others it did not. In the end it was not found to be significantly superior enough to placebo and development was stopped.

<span class="mw-page-title-main">Alnespirone</span> Antidepressant and anxiolytic drug

Alnespirone (S-20,499) is a selective 5-HT1A receptor full agonist of the azapirone chemical class. It has antidepressant and anxiolytic effects.

<span class="mw-page-title-main">Eptapirone</span> Chemical compound

Eptapirone (F-11,440) is a very potent and highly selective 5-HT1A receptor full agonist of the azapirone family. Its affinity for the 5-HT1A receptor was reported to be 4.8 nM (Ki), and its intrinsic activity approximately equal to that of serotonin.

<span class="mw-page-title-main">Umespirone</span> Anxiolytic and antipsychotic drug

Umespirone (KC-9172) is a drug of the azapirone class which possesses anxiolytic and antipsychotic properties. It behaves as a 5-HT1A receptor partial agonist (Ki = 15 nM), D2 receptor partial agonist (Ki = 23 nM), and α1-adrenoceptor receptor antagonist (Ki = 14 nM), and also has weak affinity for the sigma receptor (Ki = 558 nM). Unlike many other anxiolytics and antipsychotics, umespirone produces minimal sedation, cognitive/memory impairment, catalepsy, and extrapyramidal symptoms.

<span class="mw-page-title-main">Roxindole</span> Dopaminergic & serotonergic drug developed for schizophrenia treatment

Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed by Merck KGaA for the treatment of schizophrenia. In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects. As a result, roxindole was further researched for the treatment of depression instead. It has also been investigated as a therapy for Parkinson's disease and prolactinoma.

<span class="mw-page-title-main">Lesopitron</span> Chemical compound

Lesopitron (E-4424) is a selective full agonist of the 5-HT1A receptor which is structurally related to the azapirones. In 2001 it was under development by Esteve as an anxiolytic for the treatment of generalized anxiety disorder (GAD). It made it to phase II clinical trials but was apparently discontinued as no new information on lesopitron has surfaced since.

<span class="mw-page-title-main">Repinotan</span> Chemical compound

Repinotan (BAYx3702), an aminomethylchroman derivative, is a selective 5-HT1A receptor full agonist with high potency and efficacy. It has neuroprotective effects in animal studies, and was trialed in humans for reducing brain injury following head trauma. It was subsequently trialed up to phase II for treatment of stroke, but while side effects were mild and consisted mainly of nausea, repinotan failed to demonstrate sufficient efficacy to justify further clinical trials. However, repinotan continues to be investigated for other applications, and was found to be effective at counteracting the respiratory depression produced by morphine, though with slight reduction in analgesic effects.

<span class="mw-page-title-main">Osemozotan</span> Pharmaceutical drug

Osemozotan (MKC-242) is a selective 5-HT1A receptor agonist with some functional selectivity, acting as a full agonist at presynaptic and a partial agonist at postsynaptic 5-HT1A receptors. 5-HT1A receptor stimulation influences the release of various neurotransmitters including serotonin, dopamine, norepinephrine, and acetylcholine. 5-HT1A receptors are inhibitory G protein-coupled receptor.

References

  1. Gleeson S, Barrett JE (October 1990). "5-HT1A agonist effects on punished responding of squirrel monkeys". Pharmacology, Biochemistry, and Behavior. 37 (2): 335–7. doi:10.1016/0091-3057(90)90344-H. PMID   1981937. S2CID   23488390.
  2. Singh A, Lucki I (April 1993). "Antidepressant-like activity of compounds with varying efficacy at 5-HT1A receptors". Neuropharmacology. 32 (4): 331–40. doi:10.1016/0028-3908(93)90153-T. PMID   8497336. S2CID   38611829.
  3. Rickels K, Derivan A, Kunz N, Pallay A, Schweizer E (June 1996). "Zalospirone in major depression: a placebo-controlled multicenter study". Journal of Clinical Psychopharmacology. 16 (3): 212–7. doi:10.1097/00004714-199606000-00004. PMID   8784652.