Pharmacodynamics
Risperidone has been classified as a "qualitatively atypical" antipsychotic agent with a relatively low incidence of extrapyramidal side effects (when given at low doses) that has more pronounced serotonin antagonism than dopamine antagonism. Risperidone contains the functional groups of benzisoxazole and piperidine as part of its molecular structure. Although not a butyrophenone, it was developed with the structures of benperidol and ketanserin as a basis. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, and 5-HT2A, linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with typical antipsychotics.[55]
It has been found that D -amino acid oxidase, the enzyme that catalyses the breakdown of D -amino acids (e.g. D -alanine and D -serine — the neurotransmitters) is inhibited by risperidone.[56]
Risperidone acts on the following receptors:
Dopamine receptors: This drug is an antagonist of the D1 (D1, and D5) as well as the D2 (D2, D3 and D4) family receptors, with 70-fold selectivity for the D2 family. It has "tight binding" properties, which means it has a long half-life. Like other antipsychotics, risperidone blocks the mesolimbic pathway, the prefrontal cortex limbic pathway, and the tuberoinfundibular pathway in the central nervous system. Risperidone may induce extrapyramidal side effects, akathisia and tremors, which is associated with diminished dopaminergic activity in the striatum. It can also cause sexual side effects, galactorrhoea, infertility, gynecomastia, and, with chronic use, reduced bone mineral density leading to breaks, all of which are associated with increased prolactin secretion.[55]
Alpha α1 adrenergic receptors: This action accounts for the orthostatic hypotensive effects and perhaps some of the sedating effects of risperidone.[55]
Alpha α2 adrenergic receptors: Risperidone's action at these receptors may cause greater positive, negative, affective, and cognitive symptom control.[57]
Histamine H1 receptors: effects on these receptors account for its sedation and reduction in vigilance. This may also lead to drowsiness and weight gain.[55]
5HT2A receptor Risperidones atypicality is comparably strong, speaking about how strong this molecule is binding to 5HT2A receptors over dopaminereceptors, then the strongest substance clozapine in this regard, but differs in its selectivity to bind less strong to 5HT2A-receptors in general, but with an approximately 4-fold ratio for it.
So from the three atypicalls with being most prominent for their 5HT2A-receptorblockade (risperidone, olanzapine and clozapine), risperidone takes first place in its selectivity in a dose per dose comparison to olanzapine (20mg to 6mg, with a receptor occupation of 93 to 95% respectively). Clozapine here, takes the third place comparised in chlorpromazine-equivalents.[58][59] [60][61]
Voltage-gated sodium channels: Because it accumulates in synaptic vesicles, Risperidone inhibits voltage-gated sodium channels at clinically used concentrations.[62]
