SM-9018
SM-9018 Uses, Dosage, Side Effects, Food Interaction and all others data.
SM-9018 is an atypical or second-generation antipsychotic of the azapirone family that antagonizes serotonin 5HT2A receptors and dopamine D2 receptors. It also displays affinity towards 5HT1A receptors as a partial agonist. Dainippon Sumitomo Pharma developed perospirone in Japan in 2001 for the treatment of acute schizophrenia and bipolar mania as well as chronic schizophrenia. It is commonly present as the hydrated hydrochloride salt form. Classified as a neuroleptic agent, perospirone is shown to be effective against positive, negative and general symptoms in patients with schizophrenia . It is also shown to be less associated with extrapyramidal symptoms as a side effect compared to Haloperidol.
SM-9018 is a serotonin 5-HT2 receptor inverse agonist and dopamine D2 receptor antagonist based on receptor binding experiments that binds to both receptors with high affinity. SM-9018 is also a partial agonist at 5-HT1A receptors which are autoreceptors that stimulate the uptake of 5-HT and inhibit 5-HT release . It also interacts with D4 receptors and α₁-adrenergic receptors as an antagonist, as well as histamine H1 receptor an inverse agonist. Binding to these receptors may explain sedative and hypotensive actions. SM-9018 binds to D1 receptors with low affinity and minimal clinical significance .
| Trade Name | SM-9018 |
| Generic | Perospirone |
| Perospirone Other Names | Perospirone, SM-9018 |
| Type | |
| Formula | C23H30N4O2S |
| Weight | Average: 426.58 Monoisotopic: 426.208947396 |
| Protein binding | Plasma protein binding ratio is 92% with extensive binding to serum albumin and α1-acid glycoprotein . |
| Groups | Experimental |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
For the treatment of schizophrenia and acute cases of bipolar mania.
How SM-9018 works
Antagonism at D2 receptors is believed to relieve the positive symptoms of schizophrenia such as delusions, hallucinations, and thought disorders. SM-9018 targets the mesolimbic patway to reverse the overactivity of the dopaminergic signalling via D2 receptors . 5-HT2A antagonism is thought to allevaite the negative symptoms and cognitive impairments of schizophrenia. These receptors are Gi/Go coupled receptors that lead to decreased neurotransmitter release and neuronal inhibition when activated, thus play a role in dopamine release regulation. SM-9018 targets these receptors in the nigrostriatal pathway to reduce dopamine release and function. In contrast, 5-HT2A receptor antagonism may improve the negative symptoms by enhancing dopamine and glutamate release in the mesocortical pathway . 5-HT1A receptor activation further inhibits the release of 5-HT into the synaptic cleft.
Toxicity
Frequently experienced adverse effects include extrapyramidal symptoms, insomnia, and drowsiness. More serious adverse effect include neuroleptic malignant syndrome . Oral LD50 value in rats is 870 mg/kg .
Volume of Distribution
The mean volume of distribution following oral administration of 32 mg/day of perospirone is 1733L, with values ranging from 356-5246 L. It is shown to cross the placenta and be secreted into milk in pregnant rats .
Elimination Route
SM-9018 is rapidly absorbed following oral administration with the time to reach peak plasma concentration of 0.8 to 1.5 hours. A single oral dose of 8mg perospirone results in peak plasma concentration of 5.7 ug/L . SM-9018 is not reported to be accumulated after repeated dosing.
Half Life
The elimination half life is approximately 1.9 hours following oral ingestion of 8mg perospirone .
Clearance
Apparent clearance rate is approximately 425.5 ± 150.3 L/h in patients receiving a single oral dose of 8mg perospirone .
Elimination Route
SM-9018 is mainly excreted via renal elimination. 0.4% of of total dose is excreted as unchanged drug following oral administration of 8mg perospirone .
Innovators Monograph
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