This study will use an anticholinergic pharmacological probe to examine attention network function in SCD using EEG. The overall hypothesis is that in older adults with SCD, normal cognitive performance is maintained by compensatory attention network activity, supported by enhanced cholinergic function. The investigators anticipate that SCD will be associated with greater compensatory attention network activity and that disrupting this compensatory process through anticholinergic challenge will result in a greater negative effect on attentional performance (Attention Network Test, ANT) and attention network functioning (EEG) in older adults with greater subjective cognitive concern.

Start Date01 Nov 2024

Sponsor / Collaborator

Vanderbilt University Medical Center

NCT04756232 / RecruitingEarly Phase 1IIT

Cholinergic Mechanisms of Attention in Aging

Start Date21 Apr 2022

Sponsor / Collaborator

Vanderbilt University Medical Center

NCT03914677 / Unknown statusPhase 4IIT

Pilot Study of Mecamylamine for Autonomic Dysreflexia Prophylaxis

This is a preliminary study of the antihypertensive drug mecamylamine, used in the specific circumstance of hypertension caused by autonomic dysreflexia (AD), a condition that affects people with spinal cord injury (SCI). Initially, mild sensory stimulation of subjects' legs is used to intentionally provoke AD, as reflected by blood pressure elevation during such stimulation. In subsequent testing sessions, mecamylamine is given prior to sensory stimulation, to show the effect of the drug on preventing these AD-related blood pressure elevations.

Start Date13 Jun 2019

Sponsor / Collaborator

Wayne State University (Michigan)

100 Clinical Results associated with Mecamylamine Hydrochloride

100 Translational Medicine associated with Mecamylamine Hydrochloride

100 Patents (Medical) associated with Mecamylamine Hydrochloride

2,967

Literatures (Medical) associated with Mecamylamine Hydrochloride

01 Jan 2025·BEHAVIOURAL BRAIN RESEARCH

Central cholinergic transmission modulates endocannabinoid-induced marble-burying behavior in mice

Article

Author: Rao, Laxmi ; Patel, Richa ; Patel, Chhatrapal ; Jain, Nishant Sudhir ; Kesharwani, Anuradha

Central cholinergic system and endocannabinoid, anandamide exhibits anti-compulsive-like behavior in mice. However, the role of the central cholinergic system in the anandamide-induced anti-compulsive-like behavior is still unexplored. Therefore, the present study assessed the role of central cholinergic transmission in the anandamide-induced anti-compulsive activity using a marble-burying behavior (MBB) model in mice. The modulation in the anandamide-induced effect on MBB was evaluated using mice with altered central cholinergic transmission achieved by pretreatment (i.c.v.) with various cholinergic agents like acetylcholine (ACh), acetylcholinesterase inhibitor (AChEI), neostigmine, nicotine, mAChR antagonist, atropine, and nAChR antagonist, mecamylamine. The influence of anandamide treatment on the brain AChE activity was also evaluated. The results revealed that i.c.v. injection of anandamide (10, 20 µg/mouse, i.c.v.) dose-dependently reduced MBB in mice. Moreover, anandamide in all the tested doses inhibited the brain AChE activity indicating the role of an enhanced central cholinergic transmission in its anti-compulsive-like effect . Furthermore, the anti-compulsive-like effect of anandamide (20 µg/mouse, i.c.v.) was found to be enhanced in mice centrally pre-treated with, ACh (0.1 µg/mouse, i.c.v.) or AChEI, neostigmine (0.3 µg/mouse, i.c.v.). In addition, the anandamide-induced anti-compulsive-like effect was significantly increased in mice pre-treated with a low dose of nicotine (0.1 µg/mouse, i.c.v.) while, it was attenuated by the higher dose of nicotine (2 µg/mouse, i.c.v.). On the other hand, the anandamide (20 µg/mouse, i.c.v.) induced anti-compulsive-like effect was found to be diminished in mice pre-treated with mAChR antagonist, atropine (0.1, 0.5 µg/mouse, i.c.v.) and pre-injection of nAChR antagonist, mecamylamine (0.1, 0.5 µg/mouse, i.c.v.) potentiated the anandamide induced anti-compulsive-like response in mice. Thus, the present investigation delineates the modulatory role of an enhanced central cholinergic transmission in the anandamide-induced anti-compulsive-like behavior in mice by inhibition of brain AChE or via muscarinic and nicotinic receptors mediated mechanism.

01 Dec 2024·NEUROSCIENCE

S-(+)-mecamylamine increases the firing rate of serotonin neurons and diminishes depressive-like behaviors in an animal model of stress

Article

Author: Verdugo-Díaz, L. ; Hernández-López, S. ; Hernández-González, O ; Mondragón-García, A. ; Verdugo-Díaz, L ; Ramírez-Sánchez, E. ; Garduño, J. ; Garduño, J ; Ramírez-Sánchez, E ; Francia-Ramírez, D ; Mondragón-García, A ; Hernández-González, O. ; Ortega-Tinoco, S. ; Hernández-López, S ; Rojano-Posada, Y ; Rojano-Posada, Y. ; Francia-Ramírez, D. ; Ortega-Tinoco, S

Mecamylamine, a noncompetitive blocker of nicotinic acetylcholine receptors (nAChRs), is the racemic mixture of two stereoisomers: S-(+)-mecamylamine (S-mec) and R-(-)-mecamylamine (R-mec), with distinct interactions with α4β2 nAChRs. It has been shown that mecamylamine increases glutamate release and excites serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). In this study, we separately evaluated the effects of S-mec and R-mec on 5-HT neuron excitability. S-mec (3 μM) increased firing frequency by 40 %, while R-mec (3 μM) raised it by only 22 %. S-mec acts as a positive allosteric modulator on high-sensitivity (HS) α4β2 nAChRs at glutamate terminals, enhancing spontaneous excitatory postsynaptic currents (sEPSCs) in 5-HT neurons. Conversely, R-mec decreased sEPSCs by blocking HS α4β2 nAChRs and reduced GABA-mediated inhibitory currents (sIPSCs) by blocking α7 nAChRs at GABAergic terminals. These mechanisms make S-mec more effective than R-mec in enhancing 5-HT neuron firing. Moreover, combining S-mec with TC-2559, a selective agonist of HS α4β2 nAChRs, increased firing frequency by 65 %, exceeding the effect of S-mec alone. To validate these findings, we evaluated the antidepressant effects of S-mec (1 mg/kg) combined with TC-2559 or RJR-2403, another α4β2 nAChR agonist. This combination successfully reduced depression-like behaviors, suggesting a potential treatment strategy for patients resistant to conventional antidepressants.

01 Nov 2024·PSYCHOPHARMACOLOGY

Exploring the efficacy of cholinergic agents for the treatment of psychostimulant use disorder: a systematic review

Review

Author: Mestikawy, Salah El ; Bloch, Vanessa ; Salloum, Nicolas ; Chouchana, Margot ; Icick, Romain ; Clergue-Duval, Virgile ; Vorspan, Florence ; Daumas, Stéphanie

RATIONALE:

No drugs are currently validated to treat psychostimulant use disorder (PUD). Pathophysiological studies consistently highlight the contribution of cholinergic mechanisms in psychostimulant use, including the vulnerability to PUD, paving the way for potential therapeutic strategies.

OBJECTIVES:

The aim of this systematic review is to describe and discuss the efficacy of cholinergic agents in drug trials for patients with PUD.

METHODS:

A systematic review was conducted on April 4, 2024 in MedLine, Embase and Cochrane Library databases on controlled clinical drug trial of cholinergic agents in humans with PUD, psychostimulant abuse or dependence and psychostimulant use in recent year.

RESULTS:

Twenty-eight articles were included, twenty-one on cocaine and seven on amphetamines. Cholinergic agents used in these studies were biperiden (a muscarinic antagonist), mecamylamine (a nicotinic antagonist), nicotinic agonists, acetylcholinesterase inhibitors (AChEI), or citicoline. Two types of trials were identified. There were seventeen randomized controlled clinical trials evaluating cholinergic agents on psychostimulant use reduction in outpatients seeking treatment. Additionally, we retrieved eleven short-term «proof-of-concept» laboratory trials mainly with supervised psychostimulant administration and/or triggered craving challenges. Outpatient trials were heterogeneous and for most, inconclusive. Only two studies on galantamine (AChEI) and citicoline, reported a significant reduction of cocaine consumption. «Proof-of-concept» laboratory trials showed no evidence of efficacy on the selected outcomes, notably on craving.

CONCLUSIONS:

This review does not support the current prescription of cholinergic agents to treat PUD. Replication clinical trials notably on galantamine or other AChEI, and proof-of-concept trials on comedown symptoms will be necessary to identify a potential therapeutic indication for cholinergic agents in PUD.

News (Medical) associated with Mecamylamine Hydrochloride

07 Dec 2023

·www.prnewswire.com

Tilde Sciences acquires Daraprim® and Vecamyl® from Vyera Pharmaceuticals

NEWARK, N.J., Dec. 7, 2023 /PRNewswire/ -- Tilde Sciences, a specialty pharmaceutical company, announced today that it has acquired two medicines, Daraprim® and Vecamyl® from Vyera Pharmaceuticals. Tilde Sciences expects a seamless transition from Vyera Pharmaceuticals and uninterrupted access through Optime Care, its specialty pharmacy partner. Tilde has elected to use Optime Care because of the company's commitment to provide patients and their caregivers with dedicated programs and services in support of these important drugs. If you have any questions about Daraprim® or the financial assistance programs available, call1-877-258-2033 and press 3, or visit . Eligible patients who have commercial insurance may pay as little as $0 out-of-pocket for their prescription.1 Questions related to Vecamyl® should be directed to 1-877-794-0008 or visit . About Tilde Tilde Sciences is a United States based biopharmaceutical company specializing in the development and commercialization of specialty pharmaceuticals tailored for rare diseases with significant unmet needs. For more information visit . 1 Financial assistance programs are subject to terms and conditions and patient eligibility requirements. Restrictions, including where prohibited by law, may apply. Offers are subject to change or discontinuation without notice. Financial assistance programs are not insurance nor are they intended to be a substitute for insurance. SOURCE Tilde Sciences LLC

01 Aug 2023

·www.prnewswire.com

Vyera Pharmaceuticals, LLC and Phoenixus AG Sign Asset Purchase Agreement to Sell Rights to Daraprim and Vecamyl

NEW YORK and BAAR, Switzerland, Aug. 1, 2023 /PRNewswire/ -- Vyera Pharmaceuticals, LLC ("Vyera") and Phoenixus AG ("Phoenixus") today announced that they have entered into an Asset Purchase Agreement related to Daraprim and Vecamyl. The aggregate consideration to be paid for the sale and transfer of the purchased assets and the assignment of the certain contracts, subject to adjustment, shall be $650,000 together with the assumption of post-closing liabilities. The closing of the transaction is subject to satisfaction of certain conditions, including without limitation approval of the United States Bankruptcy Court for the District of Delaware with which Vyera and Phoenixus, together with affiliated parties, have filed voluntary petitions for relief under Chapter 11 of Title 11 of the United States Code and have elected to proceed under Subchapter V thereunder. The bankruptcy cases are jointly administered under Case No. 23-10605 (JKS). As part of the Subchapter V proceedings, Vyera filed a motion seeking authorization of its proposed bidding procedures under which to conduct its 363 sale. Additional information about this process and the proposed asset sale, as well as other documents relating to Vyera's Subchapter V proceedings, is available through Vyera's claims and noticing agent's website: . DLA Piper LLP is serving as the Vyera's legal counsel. SierraConstellation Partners LLC is serving as Chief Restructuring Officer and financial advisor, and Alvarez and Marsal Securities LLC is serving as investment banker. For more information about the sale process, interested parties should contact Alvarez and Marsal Securities LLC. About Daraprim DARAPRIM is a prescription medication that contains pyrimethamine for the treatment of toxoplasmosis when used with a sulfonamide (e.g., sulfadoxine). Toxoplasmosis is a serious, sometimes fatal infection caused by the Toxoplasma gondii (T. gondii) parasite, one of the most common parasites in the world. About Vecamyl VECAMYL® (mecamylamine HCI) is indicated for the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension. About Vyera Vyera is a United States based biopharmaceutical company committed to developing and commercializing treatments that address serious and rare diseases with high unmet medical needs. Vyera supports programs that offer financial assistance to patients in need and gives discounts to organizations that provide care to underserved populations. Vyera's research and development efforts focus on novel treatment options for toxoplasmosis and other rare or serious health conditions. . About Phoenixus AG Phoenixus AG is a Swiss based global biopharmaceutical enterprise using a virtual pharma and centralized services development model to reduce the risk, costs and timing of product development across its portfolio companies. Forward-Looking Statements This press release contains certain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and as that term is defined in the Private Securities Litigation Reform Act of 1995, that involve risks, uncertainties, and assumptions that are difficult to predict. Buyer and Vyera and Phoenixus (collectively, the "Companies") intend that such forward-looking statements be subject to the safe harbors created thereby. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as "believes," "hopes," "intends," "estimates," "expects," "projects," "plans," "anticipates" and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. The Companies' forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i) the sufficiency of the Companies' cash position, (ii) the Companies' ability to raise additional capital to fund its operations, (iii) the Companies' ability to meet its debt obligations, if any, (iv) the Companies' ability to enter into partnership or licensing arrangements with third parties, (v) the Companies' ability to identify patients to enroll in its clinical trials in a timely fashion, (vi) the Companies' ability to achieve approval of a marketable product, (vii) the design, implementation and conduct of the Companies' clinical trials, (viii) the results of the Companies' clinical trials, including the possibility of unfavorable clinical trial results, (ix) the market for, and marketability of, any product that is approved, (x) the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Companies' products, (xi) regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii) general economic and business conditions, (xiii) changes in foreign, political, and social conditions, and (xiv) various other matters, many of which are beyond the Companies' control. Except as required by law, neither Company undertakes any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release. Media Contact [email protected] SOURCE Vyera Pharmaceuticals

Patent Infringement

100 Deals associated with Mecamylamine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00611	Mecamylamine Hydrochloride	C02BB01	DB00657

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hypertension	US	Targacept, Inc.	01 Mar 1956

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic macular oedema	Phase 2	US	CoMentis, Inc.	01 Sep 2007
Wet age-related macular degeneration	Phase 2	BR	CoMentis, Inc.	01 Mar 2007
Wet age-related macular degeneration	Phase 2	CZ	CoMentis, Inc.	01 Mar 2007
Wet age-related macular degeneration	Phase 2	MX	CoMentis, Inc.	01 Mar 2007
Wet age-related macular degeneration	Phase 2	PL	CoMentis, Inc.	01 Mar 2007
Wet age-related macular degeneration	Phase 2	RU	CoMentis, Inc.	01 Mar 2007
Wet age-related macular degeneration	Phase 2	UA	CoMentis, Inc.	01 Mar 2007
Depressive Disorder, Major	Phase 2	-	Targacept, Inc.	01 Feb 2005

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SFN2019	Not Applicable	-	-	RJR-2403	swhryfhurz(wmipwbxnyr) = increased tdhtdqcpwe (iatewubfxp ) View more	-	20 Oct 2019
				Dihydro-β-eritroidine
NCT00563797 (CTgov)	Phase 3	Alcoholism \| Depressive Disorder	21	Placebo (Placebo)	koplllmyjx(zgfchlyfpv) = odrwdjypgk zkkpavwsgu (msqpzuuoxq, xufamupdkv - bkslqtytuf) View more	-	18 Apr 2016
				Mecamylamine (Mecamylamine)	koplllmyjx(zgfchlyfpv) = knzgcputnw zkkpavwsgu (msqpzuuoxq, slkwgongqo - wqwdjrzcvt) View more
NCT00773812 (Pubmed \| J Child Adolesc Psychopharmacol)	Phase 1	Autism Spectrum Disorder	20	Placebo	unmdttjuew(rtyjyhaijj) = constipation nyvdeovron (hvxxemogmb )	Negative	01 Jun 2012
				Mecamylamine
NCT00414206 (CTgov)	Phase 2	Wet age-related macular degeneration	343	Mecamylamine (1% Mecamylamine)	mrmjjjhptn(amsvovunjt) = hptlgzolui mtuqzzfbbj (gcgwjrwkwj, dirufnjqpd - yzguuveuio) View more	-	23 Nov 2010
				Mecamylamine (0.3% Mecamylamine)	mrmjjjhptn(amsvovunjt) = whzmtltqpq mtuqzzfbbj (gcgwjrwkwj, fkqxkgdlty - rivxiayohi) View more
NCT00536692 (Pubmed \| Am J Ophthalmol)	Phase 1/2	Diabetic macular oedema	-	Topical Mecamylamine	dpagcetnyz(llbbmnepbx) = sjobbdatsd veelfcbukb (lhsjexocwl )	-	01 May 2010
SFN2004	Not Applicable	-	-	Nicotine-pump implanted rats	hidmjshgnm(pgysqlzfuc) = dwkvtprafp yhmjhooftd (bnzebexpmj )	-	26 Oct 2004
				Mecamylamine	hidmjshgnm(pgysqlzfuc) = abkumagcfv yhmjhooftd (bnzebexpmj )

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