Zimelidine (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
,
BAN) (brand names Zimeldine, Normud, Zelmid) was one of the first
selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracellul ...
(SSRI)
antidepressants to be marketed. It is a pyridylallylamine, and is structurally different from other antidepressants.
Zimelidine was developed in the late 1970s and early 1980s by
Arvid Carlsson
Arvid Carlsson (25 January 1923 – 29 June 2018) was a Swedish neuropharmacologist who is best known for his work with the neurotransmitter dopamine and its effects in Parkinson's disease. For his work on dopamine, Carlsson was awarded the Nobe ...
, who was then working for the
Swedish
Swedish or ' may refer to:
Anything from or related to Sweden, a country in Northern Europe. Or, specifically:
* Swedish language, a North Germanic language spoken primarily in Sweden and Finland
** Swedish alphabet, the official alphabet used by ...
company
Astra AB. It was discovered following a search for drugs with structures similar to
brompheniramine
Brompheniramine, sold under the brand name Dimetapp among others, is a first-generation antihistamine drug of the propylamine (alkylamine) class. It is indicated for the treatment of the symptoms of the common cold and allergic rhinitis, such ...
(it is a
derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...
of brompheniramine), an
antihistamine
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provid ...
with antidepressant activity. Zimelidine was first sold in 1982.
While zimelidine had a very favorable safety profile, within a year and a half of its introduction, rare case reports of
Guillain–Barré syndrome
Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain oft ...
emerged that appeared to be caused by the drug, prompting its manufacturer to withdraw it from the market.
After its withdrawal, it was succeeded by fluvoxamine
Fluvoxamine, sold under the brand name Luvox and Faverin among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and obsessive–compulsive disorder ...
and fluoxetine (derived from the antihistamine diphenhydramine
Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...
) in that order, and the other SSRIs.
Mechanism of action
The mode of action is a strong reuptake inhibition of serotonin from the synaptic cleft. Postsynaptic receptors are not acted upon.
Other uses
Zimelidine was reported by Montplaisir and Godbout to be very effective for cataplexy
Cataplexy is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror. Cataplexy affects approximately 70% of people who have narcolepsy, and is ...
in 1986, back when this was usually controlled by tricyclic antidepressant
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
s, which often had anticholinergic
Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system.
These agents inhibit the parasympathetic nervous sys ...
effects. Zimelidine was able to improve cataplexy without causing daytime sleepiness.[
]
Side effects
Most often reported were:
* Dry mouth, dryness of pharyngeal and nasal membranes
* Increased sweating (hyperhidrosis
Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psycholog ...
)
* Vertigo
Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...
* Nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
Interactions
* MAO inhibitors — severe or life-threatening reactions possible
See also
*Ranitidine
Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome ...
* RTI-353
*Triprolidine
Triprolidine is an over-the-counter antihistamine with anticholinergic properties. It is used to combat the symptoms associated with allergies and is sometimes combined with other cold medications designed to provide general relief for flu-like ...
* SB-649,915
References
{{Bromine compounds
Alkene derivatives
Dimethylamino compounds
Antidepressants
AstraZeneca brands
Hepatotoxins
Organobromides
3-Pyridyl compounds
Selective serotonin reuptake inhibitors
Withdrawn drugs