Zotepine is an atypical antipsychotic drug indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 (although it has been discontinued in Germany) and Japan since 1982.
Zotepine is not approved for use in the United States, United Kingdom, Australia, Canada or New Zealand.
Medical uses
Zotepine's primary use is as a treatment for schizophrenia
although clinical trials have been conducted (with positive results) into its efficacy as an antimanic agent in patients with acute bipolar mania.
In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, zotepine demonstrated medium-strong effectivity. Less effective than
clozapine, slightly less effective than
olanzapine and
risperidone, approximately as effective as
paliperidone, and slightly more effective than
haloperidol,
quetiapine, and
aripiprazole.
Side effects
- Common
[British National Formulary 58. British Medical Association and Royal Pharmaceutical Society of Great Britain; 2009.]
- Unknown frequency
- Rare
Pharmacology
Pharmacodynamics
The antipsychotic effect of zotepine is thought to be mediated through antagonist activity at dopamine and serotonin receptors. Zotepine has a high affinity for the D
1 and D
2 receptors. It also affects the 5-HT
2A, 5-HT
2C, 5-HT
6, and 5-HT
7 receptors.
In addition, its active metabolite, norzotepine, serves as a potent norepinephrine reuptake inhibitor.
|
|
| 151 |
| 530 |
| 3621 |
| 470.5 |
| 59.5 |
| 119 |
| 700 |
| 2.7 |
| 2.6 |
| 472 |
| 29 |
| 6 |
| 12 |
| 7 |
| 5 |
| 180 |
| 5.35 |
| 106 |
| 18 |
| 140 |
| 73 |
| 77 |
| 260 |
| 71 |
| 25 |
| 5.4 |
| 11 |
| 6.4 |
| 18 |
| 248 |
| 3.21 |
| 500 |
| 1977 |
Synthesis
The reaction of 2-chloroacetophenone with 4-chlorothiophenol gives a
thioether. This is treated with
morpholine and sulfur in a Willgerodt–Kindler reaction to give a phenylacetic acid derivative after acid
hydrolysis of the amide intermediate. Cyclization of this compound in the presence of polyphosphoric acid forms the
dibenzothiepin ring system of the drug. The
enol ether, zotepine, is produced when this is treated with the chloroethyl amine and potassium carbonate in methyl isobutyl ketone as solvent. Under these conditions, the undesired product of C-alkylation is minimised.
Society and culture
Brand names
Brand names include
Losizopilon (Japan),
Lodopin (Indonesia, Japan),
Setous (Japan),
Zoleptil (Czech Republic, Portugal, Turkey, United Kingdom†),
Zotewin (India); where † indicates a formulation that has been discontinued.
See also
Further reading
