関: Chlor-Trimeton、chlorpheniramine、chlorpheniramine maleate

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/07 20:18:54」(JST)

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Chlorphenamine (INN) or chlorpheniramine (USAN, former BAN), commonly marketed in the form of chlorpheniramine maleate (Chlorphen-12^[1]), is a first-generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. Its sedative effects are relatively weak compared to other first-generation antihistamines. Chlorphenamine is one of the most commonly used antihistamines in small-animal veterinary practice. Although not generally approved as an antidepressant or anti-anxiety medication, chlorphenamine appears to have these properties as well.

Chlorphenamine is part of a series of antihistamines including pheniramine (Naphcon) and its halogenated derivatives and others including fluorpheniramine, dexchlorpheniramine (Polaramine), brompheniramine (Dimetapp), dexbrompheniramine (Drixoral), deschlorpheniramine, dipheniramine (also known as triprolidine with the trade name Actifed), and iodopheniramine.

The halogenated alkylamine antihistamines all exhibit optical isomerism, and chlorphenamine in the indicated products is racemic chlorphenamine maleate, whereas dexchlorpheniramine is the dextrorotary stereoisomer.

Serotonergic and norepinephrinergic effects[edit]

In addition to being an histamine H1 receptor antagonist, chlorphenamine has been shown to work as a serotonin-norepinephrine reuptake inhibitor or SNRI.^[2] A similar antihistamine, brompheniramine, led to the discovery of the SSRI zimelidine. Limited clinical evidence shows that it is comparable to several antidepressant medications in its ability to inhibit the reuptake of serotonin and also norepinephrine (noradrenaline).^[3] However, extensive clinical trials of its psychiatric properties in humans have not been conducted. It inhibits serotonin reuptake less than norepinephrine reuptake,^[4] however the literature is not consistent in this respect.^[5]

A study performed on Fischer 344/Brown Norway F1 hybrid rats showed that intraventricular administration of Chlorphenamine reduced fear-related behaviors and improved maze performance. It was also noted that long term administration of Chlorphenamine reduced age-related deficits in motor function.^[6]

Combination medications[edit]

Chlorphenamine is often combined with phenylpropanolamine to form an allergy medication with both antihistamine and decongestant properties. Brand names include Demazin, Allerest 12 Hour, Codral Nighttime, Chlornade, Contac 12 Hour, Exchange Select Allergy Multi-Symptom, A. R. M. Allergy Relief, Ordrine, Ornade Spansules, Teldrin, Triaminic, and Tylenol Cold/Allergy.

Chlorphenamine is combined with a narcotic (hydrocodone) in the product Tussionex, which is indicated for treatment of cough and upper respiratory symptoms associated with allergy or cold in adults and children 6 years of age and older.^[7] This combination is manufactured as a time-released formula, which allows for administration every 12 hours, versus the more common 4-to-6-hour regimen for other narcotic cough suppressants.

Chlorphenamine/dihydrocodeine immediate-release syrups are also marketed. The antihistamine is helpful in cases where allergy or common cold is the reason for the cough; it is also a potentiator of opioids, allowing enhanced suppression of cough, analgesia, and other effects from a given quantity of the drug by itself. In various places in the world, cough & cold preparations containing codeine and chlorphenamine are available.

In the drug Coricidin, chlorphenamine is combined with the cough suppressant dextromethorphan.

Adverse effects[edit]

The adverse effects include drowsiness, dizziness, confusion, constipation, anxiety, nausea, blurred vision, restlessness, decreased coordination, dry mouth, shallow breathing, hallucinations, irritability, problems with memory or concentration, tinnitus and trouble urinating.

Chemistry[edit]

Chlorphenamine, 3-(p-chlorophenyl)-3-(2-pyridyl)propyldimethylamine, is synthesized in two ways. The first is from 4-chlorbenzylcyanide, which is reacted with 2-chloropyridine in the presence of sodium amide to form 4-chlorophenyl(2-pyridyl)acetonitrile. Alkylating this with 2-dimethylaminoethylchloride in the presence of sodium amide gives γ-(4-chlorphenyl)-γ-cyano-N,N-dimethyl-2-pyridinepropanamine, the hydrolysis and decarboxylation of which lead to chlorphenamine.

D. Papa, E. Schwenk, N. Sperber, U.S. Patent 2,567,245 (1951).

The second way is from pyridine, which undergoes alkylation by 4-chlorobenzylchloride,^[8] giving 2-(4-chlorobenzyl)pyridine. Alkylating this with 2-dimethylaminoethylchloride in the presence of sodium amide gives chlorphenamine.

D. Papa, E. Schwenk, N. Sperber, U.S. Patent 2,676,964 (1954).

References[edit]

^ "Chlorphen-12".
^ Carlsson, A.; Linqvist M. (1969). "Central and peripheral monoaminergic membrane-pump blockade by some addictive analgesics and antihistamines". Journal of Pharmacy and Pharmacology 21 (7): 460–464. PMID 4390069.
^ Hellbom, E. (2006). "Chlorpheniramine, selective serotonin-reuptake inhibitors (SSRIs) and over-the-counter (OTC) treatment". Medical Hypotheses 66 (4): 689–690. doi:10.1016/j.mehy.2005.12.006. PMID 16413139.
^ Domino, E. F. (1999). "History of Modern Psychopharmacology: A Personal View With an Emphasis on Antidepressants" (pdf). Psychosomatic Medicine 61 (5): 591–598. PMID 10511010.
^ Compare, for example, Hellbom (2005) with Domino (1999)
^ Hasenöhrl, R. U.; Weth, K.; Huston, J. P. (1999). "Intraventricular infusion of the histamine H1 receptor antagonist chlorpheniramine improves maze performance and has anxiolytic-like effects in aged hybrid Fischer 344×Brown Norway rats". Experimental Brain Research 128 (4): 435–440. doi:10.1007/s002210050866. PMID 10541737.
^ "Tussionex® Pennkinetic® (hydrocodone polistirex and chlorpheniramine polistirex) Extended-Release Suspension" (pdf). UCB. 2011.
^ http://pubs.acs.org/doi/abs/10.1021/ja01181a508

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1. デキストロメトルファン乱用および中毒：臨床的特徴および診断 dextromethorphan abuse and poisoning clinical features and diagnosis
2. デキストロメトルファン中毒：治療 dextromethorphan poisoning treatment
3. 妊娠中のアレルギー疾患の認識およびマネージメント recognition and management of allergic disease during pregnancy
4. OTC咳止め・かぜ薬：小児の中毒へのアプローチ over the counter cough and cold preparations approach to pediatric poisoning
5. 成人における感冒：治療および予防 the common cold in adults treatment and prevention

English Journal

Effect of type and ratio of solubilising polymer on characteristics of hot-melt extruded orodispersible films.

Low AQ, Parmentier J, Khong YM, Chai CC, Tun TY, Berania JE, Liu X, Gokhale R, Chan SY.SourceAbbVie Pte. Ltd., 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore; Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Block S4, #02-18, Singapore 117543, Singapore. Electronic address: ariana.low@abbvie.com.
International journal of pharmaceutics.Int J Pharm.2013 Oct 15;455(1-2):138-47. doi: 10.1016/j.ijpharm.2013.07.046. Epub 2013 Jul 31.
In formulating an orodispersible film (ODF), it is important for polymer choice to strike a balance between mechanical properties and release rates. Studies have been done to study polymer combinations. However, there is a lack of a systematic study to determine key factors affecting these propertie
PMID 23916824

Effect of hyperthermia on histamine blood level and convulsive behavior in infant rats.

Gholipoor P, Saboory E, Roshan-Milani S, Fereidoni J.SourceDepartment of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. Electronic address: gholipoorpeyman@yahoo.com.
Epilepsy & behavior : E&B.Epilepsy Behav.2013 Sep 16. pii: S1525-5050(13)00397-1. doi: 10.1016/j.yebeh.2013.07.026. [Epub ahead of print]
Febrile seizures (FS), which have been extensively studied using animal models, are the most common type of convulsive events in children, but the cellular mechanisms causing FS are still unclear. Histamine has been suggested to participate in seizure control. This study investigated the effect of h
PMID 24051280

Resolution of five-component mixture using mean centering ratio and inverse least squares chemometrics.

Issa MM, Nejem RA, Shanab AM, Shaat NT.AbstractBACKGROUND: A comparative study of the use of mean centering of ratio spectra and inverse least squares for the resolution of paracetamol, methylparaben, propylparaben, chlorpheniramine maleate and pseudoephedrine hydrochloride has been achieved showing that the two chemometric methods provide a good example of the high resolving power of these techniques. Method (I) is the mean centering of ratio spectra which depends on using the mean centered ratio spectra in four successive steps that eliminates the derivative steps and therefore the signal to noise ratio is improved. The absorption spectra of prepared solutions were measured in the range of 220--280 nm. Method (II) is based on the inverse least squares that depend on updating developed multivariate calibration model. The absorption spectra of the prepared mixtures in the range 230--270 nm were recorded.
Chemistry Central journal.Chem Cent J.2013 Sep 12;7(1):152. [Epub ahead of print]
BACKGROUND: A comparative study of the use of mean centering of ratio spectra and inverse least squares for the resolution of paracetamol, methylparaben, propylparaben, chlorpheniramine maleate and pseudoephedrine hydrochloride has been achieved showing that the two chemometric methods provide a goo
PMID 24028626

「chlorpheniramine maleate」

Chlorphenamine
Systematic (IUPAC) name
	3-(4-chlorophenyl)-N,N-dimethyl-; 3-pyridin-2-yl-propan-1-amine
Clinical data
Trade names	Chlor-trimeton
AHFS/Drugs.com	monograph
MedlinePlus	a682543
Pregnancy cat.	A (AU) B (US)
Legal status	Pharmacist Only (S3) (AU) OTC (UK) OTC (US); (for oral forms)
Routes	Oral, IV, IM, SC
Pharmacokinetic data
Bioavailability	25 to 50%
Protein binding	72%
Metabolism	Hepatic (CYP2D6)
Half-life	21–27 hours
Excretion	Renal
Identifiers
CAS number	132-22-9
ATC code	R06AB04
PubChem	CID 2725
IUPHAR ligand	1210
DrugBank	DB01114
ChemSpider	2624
UNII	3U6IO1965U
KEGG	D07398
ChEBI	CHEBI:52010
ChEMBL	CHEMBL505
Chemical data
Formula	C16H19ClN2
Mol. mass	274.788 g/mol
	SMILES Clc1ccc(cc1)C(c2ncccc2)CCN(C)C;
	InChI InChI=1S/C16H19ClN2/c1-19(2)12-10-15(16-5-3-4-11-18-16)13-6-8-14(17)9-7-13/h3-9,11,15H,10,12H2,1-2H3 ; Key:SOYKEARSMXGVTM-UHFFFAOYSA-N ;
Physical data
Solubility in water	0.55 g/100 mL, liquid mg/mL (20 °C)
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マレイン酸クロルフェニラミン、クロルフェニラミンマレイン酸塩

関: Chlor-Trimeton、chlorphenamine、chlorpheniramine、chlorpheniramine polistirex、d-chlorpheniramine maleate

同: Chlor-Trimeton

「クロルフェナミン」

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英: chlorphenamine
関: クロルフェニラミンマレイン酸クロルフェニラミン chlorpheniramine maleate、クロール・トリメトン、

「Chlor-Trimeton」

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クロール・トリメトン

関: chlorphenamine、chlorpheniramine、chlorpheniramine maleate

同: chlorpheniramine maleate

[1] "Chlorphen-12".

[2] Carlsson, A.; Linqvist M. (1969). "Central and peripheral monoaminergic membrane-pump blockade by some addictive analgesics and antihistamines". Journal of Pharmacy and Pharmacology 21 (7): 460–464. PMID 4390069.

[3] Hellbom, E. (2006). "Chlorpheniramine, selective serotonin-reuptake inhibitors (SSRIs) and over-the-counter (OTC) treatment". Medical Hypotheses 66 (4): 689–690. doi:10.1016/j.mehy.2005.12.006. PMID 16413139.

[4] Domino, E. F. (1999). "History of Modern Psychopharmacology: A Personal View With an Emphasis on Antidepressants" (pdf). Psychosomatic Medicine 61 (5): 591–598. PMID 10511010.

[5] Compare, for example, Hellbom (2005) with Domino (1999)

[6] Hasenöhrl, R. U.; Weth, K.; Huston, J. P. (1999). "Intraventricular infusion of the histamine H1 receptor antagonist chlorpheniramine improves maze performance and has anxiolytic-like effects in aged hybrid Fischer 344×Brown Norway rats". Experimental Brain Research 128 (4): 435–440. doi:10.1007/s002210050866. PMID 10541737.

[7] "Tussionex® Pennkinetic® (hydrocodone polistirex and chlorpheniramine polistirex) Extended-Release Suspension" (pdf). UCB. 2011.

[8] ttp://pubs.acs.org/doi/abs/10.1021/ja01181a508

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chlorphenamine