Risperidone - Pharmacology

Pharmacology

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 is unique among most other atypicals in that it has high affinity for the D2 receptor (also known as 'tight binding') whereas most other atypicals have 'loose binding' of the D2 receptor. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT_2C, linked to weight gain, 5-HT_2A, linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with the typical neuroleptics.

• 5-HT_1A serotonin receptors antagonist (Ki = 420nM)
• 5-HT_1D serotonin receptors antagonist (Ki = 100nM)
• 5-HT_2A serotonin receptors antagonist (Ki = 0.16nM)
• 5-HT_2C receptors antagonist (Ki = 26nM)
• 5-HT₇ irreversible antagonist
• D₁ dopaminergic receptors (Ki = 536 nM)
  • D₁ receptor antagonist
  • D₅ receptor antagonist
• D₂ dopaminergic receptors (Ki = 3.13 nM)
  • D₂ receptor antagonist
  • D₃ receptor inverse agonist
  • D₄ receptor antagonist
• α₁ adrenergic antagonist; all subtypes (Ki = 0.8 nM)
  • α_1A
  • α_1B
  • α_1D
• α₂ adrenergic antagonist; all subtypes (Ki = 7.54 nM)
  • α_2A
  • α_2B
  • α_2C
• H₁ histamine receptor antagonist (Ki = 2.23 nM)

It reaches peak plasma levels quickly, regardless of whether it is administered as a liquid or pill. Risperidone is metabolized fairly quickly, so the potential for nausea subsides usually in two to three hours. However, the active metabolite, 9-hydroxy-risperidone, which has similar pharmacodynamics to risperidone, remains in the body for much longer, and has been developed as an antipsychotic in its own right, called paliperidone.

An intramuscular preparation, marketed as Risperdal Consta, can be given once every two weeks. It is slowly released from the injection site. This method of administration may be used on sanctioned patients who are declining, or consenting patients who may have disorganized thinking and cannot remember to take their daily doses. Doses range from 12.5 to 50 mg given as an intramuscular injection once every two weeks.