Alstonine is an indoloquinolizidine

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

and putative

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...

constituent of various plant species including ''

Alstonia boonei ''Alstonia boonei'' is a very large, deciduous, tropical-forest tree belonging to the family Apocynaceae. It is native to tropical West Africa, with a range extending into Ethiopia and Tanzania. Its common name in the English timber trade is che ...

'', ''

Catharanthus roseus ''Catharanthus roseus'', commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a species of flowering plant in the family Apocynaceae. It is native and endemic to M ...

'', ''

Picralima nitida ''Picralima'' is a plant genus in the family Apocynaceae, first described as a genus in 1896. It contains only one known species, ''Picralima nitida'', native to tropical Africa (Benin, Ghana, Ivory Coast, Nigeria, Gabon, Cameroon, Cabinda, Cent ...

'', '' Rauwolfia caffra'' and '' Rauwolfia vomitoria''. In preclinical studies alstonine attenuates

MK-801 Dizocilpine ( INN), also known as MK-801, is a pore blocker of the ''N''-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is ...

-induced hyperlocomotion, working memory deficit and social withdrawal. It also possesses

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

-like effects in preclinical studies, attenuates amphetamine-induced lethality and stereotypy as well as

apomorphine Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non- selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antag ...

-induced stereotypy, and attenuates

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

-induced

catalepsy Catalepsy (from Ancient Greek , , "seizing, grasping") is a nervous condition characterized by muscular rigidity and fixity of posture regardless of external stimuli, as well as decreased sensitivity to pain. Signs and symptoms Symptoms in ...

. These effects appear to be mediated by stimulation of the 5-HT_2C receptor. In addition, alstonine, similarly to

clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...

, indirectly inhibits the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the Synapse, pre-synaptic neuron at a synapse) or glial cell after it has performed its function of ...

of glutamate in

hippocampal The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, an ...

slices. Unlike clozapine however, the effect of which is abolished by the D₂ receptor agonist apomorphine, alstonine requires 5-HT_2A and 5-HT_2C receptors to produce this effect, as it is abolished by antagonists of these receptors. Also unlike clozapine, alstonine lacks pro-convulsant activity in mice.

References

Indoloquinolizines Antipsychotics Indole alkaloids Serotonin receptor agonists Methyl esters Heterocyclic compounds with 5 rings Quaternary ammonium compounds {{nervous-system-drug-stub

See also

References