WordNet

a complex consisting of an organic base in association with hydrogen chloride

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/26 21:26:13」(JST)

wiki en

Mecamylamine (Inversine) is a nonselective and noncompetitive antagonist of nicotinic acetylcholine receptors that was introduced in the 1950s as an antihypertensive drug.^[1]

Chemically, it is a secondary aliphatic amine, with a pK_aH of 11.2^[2]

Pharmacology and Clinical Applications

Mecamylamine has been used as an orally-active ganglionic blocker in treating autonomic dysreflexia and hypertension,^[3] but, like most ganglionic blockers, it is more often used now as a research tool.

Mecamylamine is also sometimes used as an anti-addictive drug to help people stop smoking tobacco,^[4] and is now more widely used for this application than it is for lowering blood pressure. This effect is thought to be due to its blocking α3β4 nicotinic receptors in the brain. It has also been reported to bring about sustained relief from tics in Tourette's Disorder when a series of more usually used agents had failed [22].

In a recent double-blind, placebo-controlled Phase II trial in Indian patients with major depression, (S)-mecamylamine (TC-5214) appeared to have efficacy as an augmentation therapy. This is the first substantive evidence that shows that compounds where the primary pharmacology is antagonism to neuronal nicotinic receptors will have antidepressant properties.^[5]^[6] TC-5214 is currently in Phase III of clinical development as an add-on treatment and on stage II as a monotherapy treatment for major depression. The first results reported from the Phase III trials showed that TC-5214 failed to meet the primary goal and the trial did not replicate the effects that had been encouraging in the Phase II trial.^[7]^[8] Development is funded by Targacept and AstraZeneca.^[9] It did not produce meaningful, beneficial results on patients as measured by changes on the Montgomery-Asberg Depression Rating Scale after eight weeks of treatment as compared with placebo.

(S)-(+)-Mecamylamine dissociates more slowly from α4β2 and α3β4 receptors than does the (R)-(-)-enantiomer.^[10]

A large SAR study of mecamylamine and its analogs was reported by a group from Merck in 1962.^[11] Another, more recent SAR study was undertaken by Suchocki et al.^[12]

A comprehensive review of the pharmacology of mecamylamine was published in 2001.^[13]

Toxicology

LD₅₀ for the HCl salt^[14] in mice: 21 mg/kg (i.v.); 37 mg/kg (i.p.); 96 mg/kg (p.o.).^[15]

References

^ Bacher I, Wu B, Shytle DR, George TP (November 2009). "Mecamylamine - a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders". Expert Opinion on Pharmacotherapy 10 (16): 2709–21. doi:10.1517/14656560903329102. PMID 19874251.
^ L. S. Schanker et al. (1957) J. Pharmacol. Exp. Ther. 120 528.
^ T. O. Soine (1966), Textbook of Organic Medicinal and Pharmaceutical Chemistry, 5th Ed., (C. O. Wilson, O. Gisvold and R. F. Doerge, Eds.), pp. 468-546, Philadelphia: Lippincott.
^ Shytle RD, Penny E, Silver AA, Goldman J, Sanberg PR (July 2002). "Mecamylamine (Inversine): an old antihypertensive with new research directions". J Hum Hypertens 16 (7): 453–7. doi:10.1038/sj.jhh.1001416. PMID 12080428.
^ Lippiello PM, Beaver JS, Gatto GJ, et al (2008). "TC-5214 (S-(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity". CNS Neurosci Ther 14 (4): 266–77. doi:10.1111/j.1755-5949.2008.00054.x. PMID 19040552.
^ Rabenstein RL, Caldarone BJ, Picciotto MR (December 2006). "The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not beta2- or alpha7-nicotinic acetylcholine receptor subunit knockout mice". Psychopharmacology (Berl.) 189 (3): 395–401. doi:10.1007/s00213-006-0568-z. PMID 17016705.
^ John Carroll. "Key AZ/Targacept depression drug flunks first Phase III test". Fiercebiotech.com. Retrieved 2011-11-09.
^ "Targacept Shares Fall After Depression Medicine Misses Goal". News.businessweek.com. 2007-01-15. Retrieved 2011-11-09.
^ "AstraZeneca Pipeline as of the 27th of January 2011". Retrieved 2011-11-09.
^ Papke RL, Sanberg PR, Shytle RD (May 2001). "Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes". J. Pharmacol. Exp. Ther. 297 (2): 646–56. PMID 11303054.
^ C. A. Stone et al. (1962) J. Med. Pharm. Chem. 5 665-690.
^ Suchocki, J. A.; May, E. L.; Martin ,T. J.; George, C.; Martin, B. R. (1991). "Synthesis of 2-exo- and 2-endo-mecamylamine analogs. Structure-activity relationships for nicotinic antagonism in the central nervous system". Journal of Medicinal Chemistry 34 (3): 1003–1010. doi:10.1021/jm00107a019.
^ J. M. Young et al. (2001) Clin. Ther. 23 532-565.
^ In view of the time period when these data were generated, they presumably refer to the HCl salt of the racemic drug - see discussion of stereochemical issues in "Chemistry" section.
^ A. Spinks et al. (1958) Br. J. Pharmacol. Chemother. 13 501-520.

L. Barnhill (2007) letters JACAP 46 3-4

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 過敏性腸症候群に対するアロセトロン塩酸塩（Lotronex） alosetron hydrochloride lotronex for irritable bowel syndrome
2. 早産児における非経口栄養 parenteral nutrition in premature infants
3. 変形性関節症の薬物療法に対する実験的アプローチ investigational approaches to the pharmacologic therapy of osteoarthritis
4. コーガン症候群 cogans syndrome
5. 局所麻酔剤に対するアレルギー反応 allergic reactions to local anesthetics

English Journal

Potential therapeutic uses of mecamylamine and its stereoisomers.

Nickell JR1, Grinevich VP, Siripurapu KB, Smith AM, Dwoskin LP.
Pharmacology, biochemistry, and behavior.Pharmacol Biochem Behav.2013 Jul;108:28-43. doi: 10.1016/j.pbb.2013.04.005. Epub 2013 Apr 18.
Mecamylamine (3-methylaminoisocamphane hydrochloride) is a nicotinic parasympathetic ganglionic blocker, originally utilized as a therapeutic agent to treat hypertension. Mecamylamine administration produces several deleterious side effects at therapeutically relevant doses. As such, mecamylamine's
PMID 23603417

Nicotine-induced structural plasticity in mesencephalic dopaminergic neurons is mediated by dopamine D3 receptors and Akt-mTORC1 signaling.

Collo G1, Bono F, Cavalleri L, Plebani L, Mitola S, Merlo Pich E, Millan MJ, Zoli M, Maskos U, Spano P, Missale C.
Molecular pharmacology.Mol Pharmacol.2013 Jun;83(6):1176-89. doi: 10.1124/mol.113.084863. Epub 2013 Mar 29.
Although long-term exposure to nicotine is highly addictive, one beneficial consequence of chronic tobacco use is a reduced risk for Parkinson's disease. Of interest, these effects both reflect structural and functional plasticity of brain circuits controlling reward and motor behavior and, specific
PMID 23543412

Glycine- and GABA-mimetic Actions of Shilajit on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Mice.

Yin H1, Yang EJ, Park SJ, Han SK.
The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology.Korean J Physiol Pharmacol.2011 Oct;15(5):285-9. doi: 10.4196/kjpp.2011.15.5.285. Epub 2011 Oct 31.
Shilajit, a medicine herb commonly used in Ayurveda, has been reported to contain at least 85 minerals in ionic form that act on a variety of chemical, biological, and physical stressors. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial noci
PMID 22128261

Related Pictures

★リンクテーブル★

リンク元	「メカミラミン」
関連記事	「hydrochloride」

「メカミラミン」

Mecamylamine
Systematic (IUPAC) name
	(1S,2R,4R)-N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine
Clinical data
AHFS/Drugs.com	Consumer Drug Information
Legal status	℞ Prescription only;
Routes	Oral
Pharmacokinetic data
Protein binding	40%
Identifiers
CAS number	60-40-2
ATC code	C02BB01
PubChem	CID 4032
IUPHAR ligand	3990
DrugBank	DB00657
ChemSpider	5036243
UNII	6EE945D3OK
ChEMBL	CHEMBL1398031
Chemical data
Formula	C11H21N
Molecular mass	167.291 g/mol
	SMILES N([C@@]2([C@@H]1CC[C@@H](C1)C2(C)C)C)C;
	InChI InChI=1S/C11H21N/c1-10(2)8-5-6-9(7-8)11(10,3)12-4/h8-9,12H,5-7H2,1-4H3/t8-,9+,11+/m0/s1 ; Key:IMYZQPCYWPFTAG-IQJOONFLSA-N ;
(what is this?) (verify)

　　[★]

英: mecamylamine、
同: メカミン
化: 塩酸メカミラミン mecamylamine hydrochloride、塩酸メカミン mecamine hydrochloride
商: INVERSINE

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[pmid19874251-1] Bacher I, Wu B, Shytle DR, George TP (November 2009). "Mecamylamine - a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders". Expert Opinion on Pharmacotherapy 10 (16): 2709–21. doi:10.1517/14656560903329102. PMID 19874251.

[2] L. S. Schanker et al. (1957) J. Pharmacol. Exp. Ther. 120 528.

[3] T. O. Soine (1966), Textbook of Organic Medicinal and Pharmaceutical Chemistry, 5th Ed., (C. O. Wilson, O. Gisvold and R. F. Doerge, Eds.), pp. 468-546, Philadelphia: Lippincott.

[pmid12080428-4] Shytle RD, Penny E, Silver AA, Goldman J, Sanberg PR (July 2002). "Mecamylamine (Inversine): an old antihypertensive with new research directions". J Hum Hypertens 16 (7): 453–7. doi:10.1038/sj.jhh.1001416. PMID 12080428.

[pmid19040552-5] Lippiello PM, Beaver JS, Gatto GJ, et al (2008). "TC-5214 (S-(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity". CNS Neurosci Ther 14 (4): 266–77. doi:10.1111/j.1755-5949.2008.00054.x. PMID 19040552.

[pmid17016705-6] Rabenstein RL, Caldarone BJ, Picciotto MR (December 2006). "The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not beta2- or alpha7-nicotinic acetylcholine receptor subunit knockout mice". Psychopharmacology (Berl.) 189 (3): 395–401. doi:10.1007/s00213-006-0568-z. PMID 17016705.

[7] John Carroll. "Key AZ/Targacept depression drug flunks first Phase III test". Fiercebiotech.com. Retrieved 2011-11-09.

[8] "Targacept Shares Fall After Depression Medicine Misses Goal". News.businessweek.com. 2007-01-15. Retrieved 2011-11-09.

[9] "AstraZeneca Pipeline as of the 27th of January 2011". Retrieved 2011-11-09.

[pmid11303054-10] Papke RL, Sanberg PR, Shytle RD (May 2001). "Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes". J. Pharmacol. Exp. Ther. 297 (2): 646–56. PMID 11303054.

[Stone-11] C. A. Stone et al. (1962) J. Med. Pharm. Chem. 5 665-690.

[12] Suchocki, J. A.; May, E. L.; Martin ,T. J.; George, C.; Martin, B. R. (1991). "Synthesis of 2-exo- and 2-endo-mecamylamine analogs. Structure-activity relationships for nicotinic antagonism in the central nervous system". Journal of Medicinal Chemistry 34 (3): 1003–1010. doi:10.1021/jm00107a019.

[13] J. M. Young et al. (2001) Clin. Ther. 23 532-565.

[14] In view of the time period when these data were generated, they presumably refer to the HCl salt of the racemic drug - see discussion of stereochemical issues in "Chemistry" section.

[15] A. Spinks et al. (1958) Br. J. Pharmacol. Chemother. 13 501-520.

匿名

検索

案内

案内

mecamylamine hydrochloride