cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''PDE10A''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Various cellular responses are regulated by the second messengers

cAMP Camp may refer to: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...

and

cGMP CGMP is an initialism. It can refer to: *cyclic guanosine monophosphate (cGMP) * current good manufacturing practice (cGMP) *CGMP, Cisco Group Management Protocol, the Cisco version of Internet Group Management Protocol The Internet Group Manag ...

Phosphodiesterase A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many oth ...

s, such as PDE10A, eliminate cAMP- and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime monophosphate.

Inhibitors

* AMG-579 * Balipodect (TAK-063): IC₅₀ = 300 pM * Compound 96: IC₅₀ = 700 pM, high selectivity against all other members of the PDE family * CPL500036 * Mardepodect (PF-2545920) * MK-8189 *

Papaverine Papaverine (Latin '' papaver'', "poppy") is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasms and vasospasms (especially those involving the intestines, heart, or brain), occasionally in the treatment of ...

Tofisopam Tofisopam (Emandaxin, Grandaxin, Sériel) is an anxiolytic that is marketed in several European countries. Chemically, it is a 2,3-benzodiazepine. Unlike other anxiolytic benzodiazepines (which are generally 1,4- or 1,5-substituted) however, tofi ...

Research

Preliminary evidence indicates a possible link between PDE10A expression and obesity in mice and humans. PDE10A is a regulatory protein involved in the signaling of the

striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...

, a region of the brain important for controlling movement and cognition. Dysfunction of the striatum has been linked to the development of

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

. Inhibition of PDE10A has been identified as a potential treatment for the disorder, and an inhibitor compound ( MK-8189) is as of February 2023 in Phase 2b clinical development for the treatment of schizophrenia.

Inhibitors

Research

References

Further reading