Magnetically modulated drug delivery systems
Suryakant Swain, Chinam Niranjan Patra, M. E. Bhanoji Rao in Pharmaceutical drug delivery systems and vehicles, 2018
Pharmaceutical drug targeting is considered as the approach of delivering the drugs molecules to specific receptors, targeting tissues or any other specific parts of the body to one need to target the drug molecule exclusively. Magnetic drug delivery by particulate carriers is a very efficient method of delivering a drug to localized disease site. In case of tumor targeting, microsphere can internalize by tumor cells due to its much increased phagocytic activity as compared to normal cells. The use of magnetic force for the site-specific delivery by using albumin microspheres containing magnetic appears be a promising strategy. The magnetically carried microspheres and liposomes were employed to selectively transport the curare like drugs to the muscles of one of the limbs of the cat. The magnetic microspheres are separated from non-magnetic ones by exposing the mixture to magnetic field and collecting the particles retained near the magnet. Magnetic technology is widely used for external programming of cardiac pacemakers.
Ten years that changed psychiatry
David Healy in The Psychopharmacologists III, 2020
It was by chance. Let me take you back to the beginning of the story. In 1950, I was an intern in the department of Professor Delay in Sainte-Anne. I was interested in curarization and in the curare molecule. Looking back at the early work of Claude Bernard, I found that he had found that the introduction of curare, the drug which paralyses muscles, by the rectal route permitted a light curarization that allowed muscle relaxation without causing the respiratory muscles to be paralysed. He had done this in the rabbit. I repeated this study in humans using the rectal route and have a publication on it in Science - ‘Curarisation by rectal suppository’. At that time, in all publications it was standard practice to put the names of the chiefs of the department first in the list of authors. This is why the names of Professor Delay and Pichot were at the start of an article like this, whereas today they would be at the end. Our aim with infracurarization was to relax the patient. It worked to some extent. So this was an early psychopharmacology.
How Drugs Alter Physiologic Function
Carol T. Walsh, Rochelle D. Schwartz-Bloom in Pharmacology, 2004
As described earlier (Chapter 1), evaluation of the effects of drugs on physiologic function provides a critical tool for understanding biological mechanisms. As Claude Bernard pointed out more than a century ago, the drug ‘becomes an instrument that dissects and analyzes the most delicate phenomena of the living machine.’ His studies led to understanding the unique properties of the neuromuscular junction and its inhibition by the poison curare. Commonly, these investigations lead to important new therapeutics, such as the development of tubocurarine, used as a skeletal muscle relaxant in surgery. In this chapter we will consider the properties of the peripheral nervous system, especially the autonomic component, with respect to the target sites of drugs. Using the cardiovascular system as an example, we will examine how drugs can interact with several different targets to reduce elevated blood pressure or hypertension.
Something in the Blood? A History of the Autoimmune Hypothesis regarding Myasthenia Gravis
Published in Journal of the History of the Neurosciences, 2007
From the first descriptions of myasthenia gravis (MG) in the late nineteenth century, speculation about the cause of MG has centered on the possibility of some curare-like factor circulating in the blood. The transfer of transient myasthenic symptoms from a myasthenic mother to her newborn reinforced this speculation. However, it was not until 1960, when William Nastuk and coworkers noted that serum complement correlated with the clinical course in MG, and Arthur Strauss and colleagues described antiskeletal muscle antibodies in the sera of some MG patients, that a paradigm shift occurred from prior exclusive focus on the neuromuscular junction to a broader consideration of the relevance of immunological mechanisms in myasthenia. These findings coincided with an even greater scientific revolution pioneered by Macfarlane Burnet towards cell-mediated and away from chemical immunology. The dominant immunological question of the decade 1955–1965, however, was whether human autoimmune diseases actually existed. During the next decade, 1965–1975, various diseases were accepted as being autoimmune in character, and although comparatively rare, MG became prominent among them because of a known antigen, the acetylcholine receptor, and an excellent experimental model.
Curare and the Efferent Vestibular System: An Electrophysiological Study in the Frog
Published in Acta Oto-Laryngologica, 1984
In the frog we have studied the action of d-tubocurarine on the spontaneous discharge recorded from the whole horizontal semicircular canal (HC) nerve and from single HC afferent fibres. (1) Gross activity was recorded in isolated head preparations. In each case, the spontaneous frequency was measured 6 min before and 16 min after a drop of D-tubocurarine (0.1 µl, 5.10—6M) dissolved in Ringer or after a similar drop of Ringer was injected into the perilymph near the HC ampulla. Curare elicited a significant increase of the discharge frequency in about 60 % of the preparations and a decrease in 6-8 % of the cases, whether the contralateral eighth nerve was cut or not, while Ringer had no effect. After severing of the ipsilateral eighth nerve anterior branch, curare had no significant effect on the mean resting rate (calculated from 25 preparations), while in a few cases it evoked an increase or a decrease of the discharge frequency. (2) Single afferent discharges were recorded in intact frogs. The mean frequency calculated from about 200 afferent fibres was 21.4±1.7 spikesls after curare treatment, while it was only 15.6±1.3 spikesls after Ringer injection; these two values are highly significantly different. From these results we conclude that the ampullary receptors are tonically subject to an inhibitory influence probably due to the tonic activity of the cholinergic efferent vestibular system. Moreover, the activity of the hair cells is probably also controlled by another, as yet unknown cholinergic mechanism.
Agrin-LRP4-MuSK signaling as a therapeutic target for myasthenia gravis and other neuromuscular disorders
Published in Expert Opinion on Therapeutic Targets, 2017
Kinji Ohno, Bisei Ohkawara, Mikako Ito
Introduction: Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Isaacs’ syndrome, congenital myasthenic syndromes, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. Except for sarcopenia, all are orphan diseases. In addition, the NMJ signal transduction is impaired by tetanus, botulinum, curare, α-bungarotoxin, conotoxins, organophosphate, sarin, VX, and soman to name a few. Areas covered: This review covers the agrin-LRP4-MuSK signaling pathway, which drives clustering of acetylcholine receptors (AChRs) and ensures efficient signal transduction at the NMJ. We also address diseases caused by autoantibodies against the NMJ molecules and by germline mutations in genes encoding the NMJ molecules. Expert opinion: Representative small compounds to treat the defective NMJ signal transduction are cholinesterase inhibitors, which exert their effects by increasing the amount of acetylcholine at the synaptic space. Another possible therapeutic strategy to enhance the NMJ signal transduction is to increase the number of AChRs, but no currently available drug has this functionality.
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