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Influence of Altered Extent of Regional Ischemia on in Situ End-Systolic Pressure-Volume Relationships
Published in Samuel Sideman, Rafael Beyar, Analysis and Simulation of the Cardiac System — Ischemia, 2020
David A. Kass, Paolo Marino, W. Lowell Maughan
Prior to study, autonomic reflexes were blocked with hexamethonium chloride (35 mg/kg) and bilateral cervical vagotomy. The fairly high dose of hexamethonium was used to assure adequate blockade; however, this was accompanied by substantial vasodilation and myocardial depression. Arterial pressure was supported with intravenous fluids (normal saline and hetastarch), while contractile state was enhanced by a intravenous bolus of amrinone HCl (2 mg/kg).
Cholinergic Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Vishal S. Gulecha, Manoj S. Mahajan, Aman Upaganlawar, Abdulla Sherikar, Chandrashekhar Upasani
The drugs such as hexamethonium, trimethaphan, and mecamylamine cause blockade of autonomic ganglia without causing their stimulation. In 1913, Marshall had coined the term “nicotine-paralyzing” to describe the action of TMA on ganglia. Also, Acheson and Moe had explained in detail the correlation between effects of TMA on the cardiovascular system (CVS) and autonomic ganglia. Later, bisquaternary ammonium salts were developed by Baelow and coworkers. The drug-like hexamethonium consists of six methylene groups between the two quaternary nitrogen atoms with least neuromuscular and muscarinic blocking activities. Another drug, trimethylsulfonium, similar to quaternary and bisquaternary ammonium ions, possesses ganglionic blocking actions and is a hallmark in the development of sulfonium ganglionic blocking agents, for example, trimethaphan. In 1950, secondary amine compounds as mecamylamine were introduced into therapy for hypertension (Brunton et al., 2011).
Cardiovascular Disorders in High Spinal Cord Lesions
Published in David Robertson, Italo Biaggioni, Disorders of the Autonomic Nervous System, 2019
Christopher J. Mathias, Hans L. Frankel
The therapeutic approaches in the management of autonomic dysreflexia are broadly directed to the lowering of blood pressure. The actions of drugs used are related to the pathophysiological abnormalities and these are outlined in Table 10.2, which indicates how a variety of approaches can be used to reduce autonomic activity. The afferents to the spinal cord can be blocked, and an example is the use of a local anaesthetic, such as lignocaine into the urinary bladder. The spinal cord itself may be the site of action; spinal anaesthetics, are particularly effective in preventing autonomic dysreflexia especially when associated with pregnancy. The ganglionic blocker, hexamethonium, was successfully used in the past. Like most peripherally acting drugs, it has the capacity to cause profound postural hypotension. Drugs such as clonidine do not appear to do this (Reid et al., 1977; Mathiaset al., 1979c), which may reflect its predominantly central actions in lowering blood pressure. Drugs acting directly upon blood vessels, such as glyceryl trinitrate or the calcium channel blockers, which include nifedipine, can also be used sublingually, but have the potential to cause severe hypotension. Probanthine reduces sweating but may have other side effects.
Design, stability and efficacy of a new targeting peptide for nanoparticulate drug delivery to SH-SY5Y neuroblastoma cells
Published in Journal of Drug Targeting, 2019
Rachel Huey, Dan Rathbone, Paul McCarron, Susan Hawthorne
Resomer® RG 502 H, Poly(D,L-lactide-co-glycolide)-PLGA, acid terminated (MW 7000–17,000), dichloromethane (DCM), poly(vinyl) alcohol (PVA) 87–89% hydrolysed- MW 85,000–124,000, MES hydrate, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), N-hydroxysuccinimide (NHS), trichloroacetic acid (TCA), human serum from male AB plasma (USA origin), α-cyano-4-hydroxycinnamic acid (CHCA) matrix, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), hexamethonium and mecamylamine were all purchased from Sigma-Aldrich (UK). RDP, DAS and scrambled DAS (sc-DAS) peptides were synthesised by GL Biochem (Shanghai) Ltd. Nicotinic acetylcholine receptor-α7 antibody was purchased from Santa Cruz Biotechnology, Inc. (USA). Doxorubicin hydrochloride was obtained from VWR International (Pennsylvania, USA). Tissue culture reagents and media were purchased from Gibco®/Life Technologies. Human cancer cell lines, SH-SY5Y (human neuroblastoma) and HeLa (human cervical cancer), were cultured in RPMI 1640 medium as were the normal CHO (Chinese hamster ovary) cell line. MDA-MB-231 (human breast cancer) cells were cultured in DMEM medium. Both RPMI 1640 and DMEM media were supplemented with 10% foetal bovine serum and 1% penicillin-streptomycin (5000 U ml−1/5000 µg ml−1). All other chemicals were of analytical grade.
Antimuscarinic drug therapy for overactive bladder syndrome in the elderly – are the concerns justified?
Published in Expert Opinion on Pharmacotherapy, 2019
Antimuscarinic drugs, often synonymously referred to as anticholinergic medication or ‘anticholinergics’ have been the mainstay of pharmacological treatment of OAB/UI for several decades. It should be pointed out here that anticholinergic drugs include nicotinic receptor antagonists as well such as hexamethonium, atracurium, pancuronium, dextromethorphan, and others. The drugs used for lower urinary tract dysfunction are muscarinic receptor blockers which in general have a high selectivity for muscarinic receptors and do not affect nicotinic receptors in the brain and elsewhere. This distinction should be clear in the terminology because although the terms ‘anticholinergic’ and ‘antimuscarinic’ are commonly used interchangeably, they are not the same. In this review, the author has necessarily had to retain both terms because of the descriptions in the source publications, as well as in terminology such as ‘anticholinergic burden’ and ‘serum anticholinergic activity’.
In memoriam: Alberto Zanchetti
Published in Blood Pressure, 2018
Sverre E. Kjeldsen, Krzysztof Narkiewicz, Michel Burnier, Suzanne Oparil
Alberto joined the research group of Cesare Bartorelli at the University of Milan in the 1950s and explored the neural basis of blood pressure control. This was a time when the only available treatment for severe hypertension was total abdominal sympathectomy, a radical surgical procedure associated with multiple complications and a high failure rate. Alberto and his associates took on the challenge of finding effective medical treatments for these critically ill patients and demonstrated that ganglion blockers like hexamethonium and mecamylamine effectively lowered their blood pressure and improved their survival [2]. This was the start of one of the greatest success stories of modern medicine, the development of pharmacotherapy for hypertension. Alberto went on to work with nearly all of the scores of antihypertensive drugs to come in the course of a lengthy and highly productive research career.