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 accomm ...

), 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 provides ...

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

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

and

anxiolytic An anxiolytic (; also antipanic or anti-anxiety 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 anxie ...

. The structure is related to

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

. A 2004 study suggested captodiame may be helpful in preventing

benzodiazepine withdrawal syndrome Benzodiazepine withdrawal syndrome (BZD withdrawal) is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stop ...

in people discontinuing

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

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 An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.σ₁ receptor and D₃ receptor

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

. It produces

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

-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 can ...

(BDNF) levels in the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

but not in the

frontal cortex The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove betw ...

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

. This unique action may be related to its ability to attenuate stress-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 researcher ...

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 a naturally occurring organic compound with the formula (C6H5)2CO, generally abbreviated Ph2CO. Benzophenone has been found in some fungi, fruits and plants, including grapes. It is a white solid with a low melting point and ros ...

. 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 (), with the oxygen atom replaced by sulfur atom (as implied by the '' thio-'' prefix). The properties of urea and thiourea differ s ...

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)2 (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 guanidiniu ...

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 biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

, 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