Captodiame (

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 ...

), also known as captodiamine, is 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 ...

sold under the trade names Covatine, Covatix, and Suvren which is used as a sedative and

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

. The structure is related to

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 ...

. A 2004 study suggested captodiame may be helpful in preventing

benzodiazepine withdrawal syndrome Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a p ...

in people discontinuing benzodiazepine treatment.Free full text with registration
/ref> In addition to its actions as an antihistamine, captodiamine has been found to act as a 5-HT_2C receptor antagonist and σ₁ receptor and D₃ receptor agonist. It produces antidepressant-like effects in rats. However, captodiamine is unique among antidepressant-like drugs in that it increases

brain-derived neurotrophic factor Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canon ...

(BDNF) levels in the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

but not in the frontal cortex or

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

. This unique action may be related to its ability to attenuate

stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...

-induced

anhedonia Anhedonia is a diverse array of deficits in hedonic function, including reduced motivation or ability to experience pleasure. While earlier definitions emphasized the inability to experience pleasure, anhedonia is currently used by researchers t ...

and corticotropin-releasing factor (CRF) signaling in the hypothalamus.

Synthesis

The oxygen atom in these molecules can in many cases be dispensed with as well; substitution of sulfur for nitrogen affords a molecule whose salient biologic properties are those of a sedative and tranquilizer. Captodiamine synthesis

Friedel-Crafts acylation of the n-butyl ether of thiophenol with

benzoyl chloride Benzoyl chloride, also known as benzenecarbonyl chloride, is an organochlorine compound with the formula . It is a colourless, fuming liquid with an irritating odour, and consists of a benzene ring () with an acyl chloride () substituent. It is ...

gives the corresponding

benzophenone Benzophenone is the organic compound with the formula (C6H5)2CO, generally abbreviated Ph2CO. It is a white solid that is soluble in organic solvents. Benzophenone is a widely used building block in organic chemistry, being the parent diarylket ...

. Reduction of the ketone with zinc/NaOH followed by treatment with HCl in ether affords the benzhydryl chloride. Displacement of the halogen with

thiourea Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), except that the oxygen atom is replaced by a sulfur atom (as implied by the ''thio-'' prefix); however, the properties of urea a ...

gives, by reaction of the last at its most nucleophilic center, the

isothiouronium In organic chemistry, isothiouronium is a functional group with the formula SC(NH2)2sup>+ (R = alkyl, aryl) and is the acid salt of isothiourea. The H centres can also be replaced by alkyl and aryl. Structurally, these cations resemble guanid ...

salt. Hydrolysis of the salt leads to the sulfur analog of a benzhydrol. Alkylation of the sodium salt of this last with ''N''-(2-chloroethyl)dimethylamine affords captodiame.

References

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

, titlestyle = background:#ccccff , list1 = {{Dopamine receptor modulators {{Histamine receptor modulators {{Muscarinic acetylcholine receptor modulators {{Serotonin receptor modulators {{Sigma receptor modulators 5-HT2C antagonists Antihistamines Anxiolytics Dopamine agonists H1 receptor antagonists Muscarinic antagonists Sedatives Sigma agonists Thioethers

Synthesis

See also

References