Zimelidine
Encyclopedia
Zimelidine was the first selective serotonin reuptake inhibitor
(SSRI) antidepressant
to be marketed. It is a pyridylallylamine, and is structurally different from other antidepressants.
Zimelidine was developed in the early 1980s by Arvid Carlsson
, who was then working for the Swedish
company Astra AB
. It was discovered following a search for drugs with structures similar to brompheniramine
(it is a derivative
of brompheniramine
), an antihistamine
with antidepressant activity. Zimelidine was first sold in 1982.
Zimelidine has been banned worldwide due to serious, sometimes fatal, cases of central and/or peripheral neuropathy known as Guillain-Barré syndrome
and due to a peculiar hypersensitivity reaction involving many organs including skin exanthem
a, flu
-like symptoms, arthralgia
s, and sometimes eosinophilia
. Additionally, zimelidine was charged to cause an increase in suicidal ideation and/or attempts among depressive patients. After its ban, it was succeeded by fluvoxamine
and fluoxetine
(derived from the antihistamine
diphenhydramine
) in that order, and the other SSRIs.
from the synaptic cleft. Postsynaptic receptors are not acted upon.
in 1986, back when this was usually controlled by tricyclic antidepressant
s, which often had anticholinergic
effects. Zimelidine was able to improve cataplexy without causing daytime sleepiness.
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
(SSRI) antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
to be marketed. It is a pyridylallylamine, and is structurally different from other antidepressants.
Zimelidine was developed in the early 1980s by Arvid Carlsson
Arvid Carlsson
Arvid Carlsson is a Swedish scientist who is best known for his work with the neurotransmitter dopamine and its effects in Parkinson's disease...
, who was then working for the Swedish
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
company Astra AB
AstraZeneca
AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...
. It was discovered following a search for drugs with structures similar to brompheniramine
Brompheniramine
Brompheniramine , commonly marketed as its salt brompheniramine maleate is an antihistamine drug of the propylamine class...
(it is a derivative
Derivative (chemistry)
In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...
of brompheniramine
Brompheniramine
Brompheniramine , commonly marketed as its salt brompheniramine maleate is an antihistamine drug of the propylamine class...
), an antihistamine
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
with antidepressant activity. Zimelidine was first sold in 1982.
Zimelidine has been banned worldwide due to serious, sometimes fatal, cases of central and/or peripheral neuropathy known as Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
and due to a peculiar hypersensitivity reaction involving many organs including skin exanthem
Exanthem
An exanthem is a widespread rash usually occurring in children. Exanthems can be caused by toxins or drugs, microorganisms, or can result from autoimmune disease.It can be contrasted with an enanthem.-Types:...
a, flu
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
-like symptoms, arthralgia
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
s, and sometimes eosinophilia
Eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
. Additionally, zimelidine was charged to cause an increase in suicidal ideation and/or attempts among depressive patients. After its ban, it was succeeded by fluvoxamine
Fluvoxamine
Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...
and fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
(derived from the antihistamine
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
diphenhydramine
Diphenhydramine
Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason...
) in that order, and the other SSRIs.
Mechanism of action
The mode of action is a strong reuptake inhibition of serotoninSerotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
from the synaptic cleft. Postsynaptic receptors are not acted upon.
Other uses
Zimelidine was reported by Montplaisir and Godbout to be very effective for cataplexyCataplexy
Cataplexy is a sudden and transient episode of loss of muscle tone, often triggered by emotions. It is a rare disease , but affects roughly 70% of people who have narcolepsy...
in 1986, back when this was usually controlled by tricyclic antidepressant
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s, which often had anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
effects. Zimelidine was able to improve cataplexy without causing daytime sleepiness.
Side effects
Most often reported were:- Dry mouth, dryness of pharyngealPharynxThe human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...
and nasal membranes - Increased sweating (hyperhidrosisHyperhidrosisHyperhidrosis is the condition characterized by abnormally increased perspiration, in excess of that required for regulation of body temperature.-Classification:Hyperhidrosis can either be generalized or localized to specific parts of the body...
) - VertigoVertigo (medical)Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
- NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...