Pharmacology/ Pharmacokinetics:
Pharmacology-
Ritanserin is a specific long acting- central serotinin S2-antogonist which does not affect
norephinephrine, acetylcholine, or central dopamine antagonism but does antagonise
peripheral histamine.
Ritanserin improves sleep quality, decreases fatigue, increases energy levels,
improves depressed mood and anxiety and appears to lack abuse potential.
Ritanserin 10mg twice daily also improves neuroleptic-induced akathisia in patients
resistent to traditionaltherapy (eg. anticholinergics, benzodiazepines , beta-blockers).
These actions of ritanserin have caused researchers to investigate its effects in the
treatment of anxiety, schizophrenia,alcoholism, drug abuse, depressive disorders
and Parkinsonism
Pharmacokinetics-
The oral bioavailability is about 75. Following oral administration, very little drug is
recovered unchanged in the urine after a 5mg IV dose suggesting that it is extensively
metabolised by the liver.
In a study involving nine healthy volunteers peak plasma concentration occured within
2.39 hours after oral administration. Steady state plasma concentrations are reached
within 1 week after initiating dosing and the half-life is 40 hours. Ritanserin is usually
administered with or after a meal to decrease the incidence of transcient side effects
(eg.dizziness, tiredness,lightheadeness) that have reported in 10% of the patients
Clinical studies-
A trial involving 33 patients was conducted to determine the efectiveness of ritanserin in
decreasing the negative symptoms of in type II schizophrenia over a 6 week period.
Patients initially received 10mg ritanserin. Doses were increased by 10mg increments
to 30mg as tolerated. The average total dose at the end of the study was 26mg.
Ritanserin significantly improved several negative symptoms such as facial
expressions,global affective flatenning and relationships with friends and peers and
also caused significant reduction in scores for emotional and withdrawal and
depressive mood compared to placebo. Three patients in ritanserin group dropped
out of the study because of lack of efficacy and one due to side effects(eg unrest) .
In another study, nine patients with acute schizophrenia received ritanserin 10mg
twice daily for 4 weeks. Five of the nine patients experienced a 50% decrease in
comphrensive pscychological rating scale scores,and scores for negative symptoms
also decreased from baseline. No extrapyrimidal side effects or alkasthisia that
could be attributed to ritanserin were reported.
Several studies have examined have examined the ability of ritanserin to affect the
motor symptoms of Parkinsons disease. Initial studies demonstrated that rifanserin
significantly reduced tremor. In contrast, two recent studies determined that ritanserin
(range 30mg/day) had a positive effect on dyskinesias but not tremor.
Ritanserin effect on dysthymia has been studied compared to placebo, amitryptyline
(Elavil) and imipramine ( Tohranil) . Rifanserin was superior to placebo and equal
to amitriptyline and imipramine for upto 8 weeks ( in >300)
Several studies have determined that ritanserin is effective in relieving anxiety ,
decreasing fatigue, and increasing energy in patients with generalized anxiety
disorders when compared to placebo, and ritanserin 10mg appears to have equal
efficacy to lorazepam (Ativan). The antianxiety effects occurred after 2 to 4 weeks
of treatment.
Ritaserin decreases the craving for alcohol and cocaine. One study involving 39
patients concluded that ritanserin 5mg decrased desire and craving for alcohol
but did not change the amount of alcohol intake during 14 days of study. Another
small study( n=5) suggested that patients receiving ritanserin 10mg for 28 days
not only had no desire to drink but demonstrated improvement in mood. Several
lage scale-double blind studies that will include > 900patients with various types
of alcohol dependence are currently under way.
Slow wave sleep (SWS) patterens were significantly improved in several studies
when ritaserin was given to patients with alcoholism and depressive disorders,
on study found that ritanserin did not affect SWS in 12 depressed patients.
