Neuromuscular Blocking Action Research Articles

ARUNDO DONAX L.: A SCIENTIFIC UPDATE

Arundo donax L. belongs to the family Poaceae. It has been found in the Mediterranean, North Africa, India and Pakistan. It grows in hilly locations in India. It grows up to 2100-2440 m in the Himalayas. Commonly, A. donax L. is known as Giant Reed in English and Narakata in Hindi. Traditionally it is used in the treatment of dropsy and cancer. It is the active ingredient of an Ayurveda formulation, “Virataradi Kashaya,” which is used in the treatment of urinary calculi, retention of urine and abdominal pain in homeopathy A. donax L. is used for the treatment of allergic rhinitis. A. donax L. contains many beneficial phytoconstituents such as protein, fat, total carbohydrate, fibers, lignin, α-cellulose, hemicelluloses, alkaloids (tryptamine, bufotenidine, gramine and arundamine), etc. A. donax L. has been found to possess many pharmacological properties like antibacterial and antifungal effects, anthelmintic effects, antifeedant activity, antiproliferative effect, effect on milk production and fattening performance, central nervous effect, hypotensive effect, antispasmodic effect, anti-acetylcholine effect, uterine stimulant effect and neuromuscular blocking activity. It is an essential ingredient of herbal expectorants. This review might be a vital tool for researchers who seek to work in this area.

Structural basis of the myotoxic inhibition of the Bothrops pirajai PrTX-I by the synthetic varespladib

Varespladib (LY315920) is a potent inhibitor of human group IIA phospholipase A2 (PLA2) originally developed to control inflammatory cascades of diseases associated with high or dysregulated levels of endogenous PLA2. Recently, varespladib was also found to inhibit snake venom PLA2 and PLA2-like toxins. Herein, ex vivo neuromuscular blocking activity assays were used to test the inhibitory activity of varespladib. The binding affinity between varespladib and a PLA2-like toxin was quantified and compared with other potential inhibitors for this class of proteins. Crystallographic and bioinformatic studies showed that varespladib binds to PrTX-I and BthTX-I into their hydrophobic channels, similarly to other previously characterized PLA2-like myotoxins. However, a new finding is that an additional varespladib binds to the MDiS region, a particular site that is related to muscle cell disruption by these toxins. The present results further advance the characterization of the molecular interactions of varespladib with PLA2-like myotoxins and provide additional evidence for this compound as a promising inhibitor candidate for different PLA2 and PLA2-like toxins.

A comparative study of train-of-four (TOF) count at corrugator supercilii and at adductor pollicis reflecting abdominal muscles relaxation

Introduction: Diaphragm and lateral abdominal muscles frequently show sparing effects to muscle relaxants. This study compared visual estimation of neuromuscular transmission of corrugator supercilii and adductor pollicis (AP) with electromyographic measurements of lateral abdominal wall muscles during recovery from vecuronium-induced intense neuromuscular block. Methods: 60 patients undergoing elective surgeries under general anesthesia were included. Following loss of consciousness, supramaximal stimulations were applied using electrical nerve stimlators to left 10th intercostal, ulnar and facial nerves. Electromyographic activity (EMG) of abdominal wall muscles were measured. After Inj. Vecuronium 0.1 mg/kg, Electromyographic activity measurements counted the visually detectable train-of-four (TOF) responses at corrugator supercilii and adductor pollicis. The onset time, the duration of action and quantitative measurements of neuromuscular block were done. Observations: Clinical duration of action of vecuronium almost coincided with train-of-four response at corrugators supercilii where as train-of-four recovery at adductor policis occurred late during recovery stage. Corrugators supercilii had a stronger positive correlation with abdominal muscles relaxation as compared to the adductor policies. Corrugators supercilii had a stronger correlation coefficient (0.910 vs 0.417) than adductor policis with respect to abdominal muscle. It indicated that corrugator supercilii is a better predictor than AP to measure abdominal muscle relaxation.

Role of botulinum toxin in the management of hand ulceration due to post-stroke spasticity among aged care residents.

Individuals with significant post-stroke impairments often move to residential care. The prevalence of spasticity is high among these residents. Palmar ulceration is an under-recognised complication of unmitigated post-stroke hand spasticity. The ulcerations are painful, emit offensive smell and cause significant suffering for the individuals and the carers. The aim of this article is to discuss the healing of these ulcerations by reducing spasticity in the hand muscles with botulinum toxin A (BoNTA) injection followed by dressing, splinting and hand therapy. This article discusses the epidemiology, anatomy and clinical presentations of spastic hand ulcerations and mechanisms of action of BoNTA in alleviating the ulcers and related symptoms such as pain, sweating, offensive smell, and lessening the carer burden. The primary neuromuscular blocking action of BoNTA results in the opening of the hand, allowing dressing and ease of care. The toxin provides pain relief, inhibits excessive sweat production and causes vasodilatation, ultimately resulting in healing of the ulcerations.

Effect of the phospholipase A2 inhibitor Varespladib, and its synergism with crotalic antivenom, on the neuromuscular blockade induced by Crotalus durissus terrificus venom (with and without crotamine) in mouse neuromuscular preparations

The venom of the South American rattlesnake Crotalus durissus terrificus causes an irreversible neuromuscular blockade in isolated preparations due to action of the presynaptically-acting heterodimeric phospholipase A2 (PLA2) crotoxin. Some populations of this subspecies contain, in addition to crotoxin, the toxin crotamine, which acts directly on muscle fibers. In this study we used C. d. terrificus venoms with (crot+) or without (crot-) crotamine to test whether Varespladib, a PLA2 inhibitor, is able to abrogate the neuromuscular blockade induced by these venoms comparatively with crotalic antivenom. Mouse phrenic nerve-diaphragm preparations were exposed to venoms previously incubated with two different concentrations of Varepladib or antivenom, or with a mixture of these two agents, before addition to the bath. In another experimental setting, venoms were initially added to the system, followed by the addition of Varespladib or antivenom 10, 30, or 60 min after venom. At the highest concentrations tested, Varespladib and antivenom inhibited the action of the venom >80% and >70%, respectively. With lower concentrations the inhibition of neuromuscular blockade decreased, but when low doses of the two agents were incubated together with the venom, the inhibitory effect improved, underscoring a synergistic phenomenon. When added after venom, Varespladib was able to halt the progression of the neuromuscular blockade even when added at 60 min. Antivenom exhibited a lower ability to inhibit the toxic effect of the venoms in these conditions. In conclusion, the PLA2 inhibitor Varespladib is highly effective at abrogating the neuromuscular blocking activity of crotamine-positive and crotamine-negative C. d. terrificus venoms and seems to act synergistically with antivenom.

Novel GABAA Agonist Entities: Pharmacological Investigation and Molecular Modeling Study of Thiazolo- and Thiadiazolo-[3,2-a][1,3]diazepine Analogs.

Thiazolo- and thiadiazolo-[3,2-a][1,3]diazepines and their patented derivatives, tested with diverse CNS pharmacological activities, constitute an important class of compounds for new drug development. Therefore, research efforts were continued to design, synthesize, and evaluate compounds for their ultra-short, short-acting hypnotic, anticonvulsant, and neuromuscular blocking activities. The present review provides a summary of the work accomplished by these heterocycles and their biological evaluation.

Neutralization of a bothropic PLA2-like protein by caftaric acid, a novel potent inhibitor of ophidian myotoxicity

Envenoming by snakebite is an important global health issue that has received little attention, leading the World Health Organization to naming it as neglected tropical disease. Several snakebites present serious local symptoms manifested on victims that may not be efficiently neutralized by serum therapy. Phospholipase A2-like (PLA2-like) toxins are present in Viperidae venoms and are responsible for local myotoxic activity. Herein, we investigated the association between BthTX-I toxin and caftaric acid (CFT), a molecule present in plants. CFT neutralized neuromuscular blocking and muscle-damaging activities promoted by BthTX-I. Calorimetric and light-scattering assays demonstrated that CFT inhibitor interacted with dimeric BthTX-I. Bioinformatics simulations indicated that CFT inhibitor binds to the toxin’s hydrophobic channel (HCh). According to the current myotoxic mechanism, three different regions of PLA2-like toxins have specific tasks: protein allosteric activation (HCh), membrane dockage (MDoS), and membrane rupture (MDiS). We propose CFT inhibitor interferes with the allosteric activation, which is related to the conformation change leading to the exposure/alignment of MDoS/MDiS region. This is the first report of a PLA2-like toxin fully inhibited by a compound that interacts only with its HCh region. Thus, CFT is a novel candidate to complement serum therapy and improve the treatment of snakebite.

A Review on Pharmacological Activities of Calotropis Procera

The plant Calotropis procera (Aiton) Dryand belong to the Apocynaceae family it is popularly known as “Rui” in Marathi, “ Mudar” in hindi other common name include Rubber Bush, Apple of sodom. (India & Pakistan). The bark and leaves are known to show wound healing, shows anti-Hyperglycemic effect, Analgesic, Anti pyretic, neuromuscular blocking activity, Purgative, anti-cancer activities. The phytochemistry of plant reveals presence of triterpenoids, flavonoids, cardiac glycosides, cardenolides, anthocyanins, α-amyrin, β-amyrin, lupeol, β-sitosterol, flavanols, mudarine, resins, a powerful bacteriolytic enzyme calactin, a nontoxic proteolytic enzyme calotropin, and a wax was isolated from the heartwood of Calotropis procera. The present review focuses on pharmacological activities of Calotropis procera. Keywords: Calotropis procera, anti- Hyperglycemic effect, wound healing, pharmacological activities.

Diabetes mellitus does not affect the neuromuscular blocking action of atracurium in dogs

ObjectiveTo compare the duration of action of atracurium in diabetic and nondiabetic dogs. Study designProspective, blinded, clinical study. AnimalsA total of 26 diabetic and 29 nondiabetic dogs. MethodsFollowing preanaesthetic medication and intravenous (IV) propofol induction, anaesthesia was maintained with isoflurane in oxygen. Atracurium 0.2 mg kg−1 IV was administered to provide neuromuscular blockade (NMB) and the responses (twitches; T) to train-of-four nerve stimulation were recorded by palpation and electromyography (EMG). Time to onset of NMB (from atracurium administration to loss of T4 by EMG), duration of NMB (to return of T1 by EMG) and also times to loss and return of T2–T4 were recorded. Heart rate (HR), mean arterial pressure, end-tidal isoflurane (Fe′Iso), end-tidal CO2 concentrations and oesophageal temperature were recorded at onset of NMB and when T1EMG returned. Groups were compared using t tests and Mann–Whitney U tests (p<0.05). ResultsDiabetic dogs were older (9.9±0.3 compared with 6.8±0.7 years, p=0.0003). Group parameters were similar at onset and offset of NMB apart from HR at offset, which was higher for diabetics compared to nondiabetics (114±4 compared with 100±3 beats minute−1, respectively, p=0.004), Fe′Iso was higher in the diabetic group at onset (1.3±0.03% compared with 1.2±0.04%, p=0.026) and offset (1.4±0.03% compared with 1.3±0.03%, p=0.007), and temperature was higher for diabetics at onset (37.5±0.1 °C compared with 37.0±0.2 °C, p=0.012) and offset (37.5±0.1 °C compared with 36.9±0.2 °C, p=0.004). The duration of action of atracurium(tactile) and atracurium(EMG) were similar for both groups. Conclusions and clinical relevanceThe duration of action of atracurium was similar in diabetic and nondiabetic dogs as indicated by tactile and EMG monitoring.

Central and peripheral neurotoxicity induced by the Jack Bean Urease (JBU) in Nauphoeta cinerea cockroaches

Ureases of Canavalia ensiformis are natural insecticides with a still elusive entomotoxic mode of action. We have investigated the mechanisms involved in the neurotoxicity induced by Jack Bean Urease (JBU) in Nauphoeta cinerea (Olivier). To carry out this study we have employed biochemical and neurophysiological analysis of different cockroach organ systems. The injection of the insects with JBU (0.75-6μg/g animal), although not lethal within 24h, caused significant inhibition of the brain acetylcholinesterase activity (60±5%, p<0.05, n=6). JBU (1.5μg/200μL), acetylcholine (0.3μg/200μL) or neostigmine (0.22μg/200μL), induced a positive cardiac chronotropism (∼25%) in the cockroaches (p<0.05, n=9). JBU (6μg/g) increased the insects' grooming activity (137±7%), similarly to octopamine (15μg/g) (p<0.05, n=30, respectively). Pretreating the insects with phentolamine (0.1μg/g) prevented the JBU- or octopamine-induced increase of grooming activity. JBU (6μg/g) caused 65±9% neuromuscular blockade in the cockroaches, an effect prevented by bicuculline (5μg/g) (p<0.05, n=6). JBU (6μg/g) decreased the frequency whilst increasing the amplitude of the spontaneous neural compound action potentials (1425±52.60min-1, controls 1.102±0.032mV, p<0.05, n=6, respectively). Altogether the results indicate that JBU induces behavioral alterations in Nauphoeta cinerea cockroaches probably by interfering with the cholinergic neurotransmission. The neuromuscular blocking activity of JBU suggests an interplay between acetylcholine and GABA signaling. The search for novel natural molecules with insecticide potential has become a necessity more than an alternative. Understanding the mode of action of candidate molecules is a crucial step towards the development of new bioinsecticides. The present study focused on the neurotoxicity of Canavalia ensiformis urease, a natural insecticide, in cockroaches and revealed interferences on the cholinergic, octopaminergic and GABA-ergic pathways as part of its entomotoxic mode of action.

Effects of conopeptide-containing venom from seven species of Conidae gastropoda on the chick biventer-cervicis nerve-muscle assessed using the ConoServer database.

Conotoxins in the venom of marine gastropods (genus Conus, family Conidae) have been incriminated in fatal human stingings. Conotoxins are peptides (conopeptides) which target specific classes of ion channels and block receptors involved in neuromuscular transmission. Some conopeptides also block receptors involved in neuropathic pain and one such peptide with an analgesic potency greater than that of morphine is marketed for clinical use. To determine the effects of venom from seven species of Conidae, Conus arenatus, Conus coronatus, Conus ebraeus, Conus lividus, Conus miles, Conus rattus, and Conus textile, collected in the inter-tidal zone of the Indian Ocean, East Africa, on the chick biventer-cervicis nervemuscle preparation and to assess the effects using data on conopeptide content in venom of the species examined reported in the literature and the ConoServer database. Only venom extracts from C. arenatus and C. textile, blocked twitch responses and produced depolarization and contracture of slow fibers of the stimulated chick nerve-muscle preparation. This is the first study showing that venom from C. arenatus is a potent inhibitor of neuromuscular transmission. However, in the case of C. textile, a species associated with fatal human stingings, the inhibitor activity was ~ 3-fold greater. These results are consistent with the occurrence of specific α-conopeptides, namely α-4/6-CtxTxID in C. textile and α-CtxArIB in C. arenatus targeting acetylcholine receptors at the neuromuscular junction. Information extractable from the ConoServer database was of limited value for evaluation of our findings since all the species examined contain numerous conopeptides, the majority of which have not been characterized pharmacologically or for which even the gene superfamily is unknown. Venom from C. textile, C. arenatus, C. coronatus, C. ebraeus, and C. rattus produced an initial facilitation of the twitch response similar to that produced by neostigmine. Venom from C. lividus and C. miles had no effect on twitch responses and did not depolarize slow fibers even at high concentrations. Using the chick biventer-cervicis nerve-muscle preparation, which contains both twitch and slow muscle fibers, a neuromuscular blocking and muscle depolarizing action could be demonstrated in venom extracts from C. textile, a Conus species associated with fatal human stingings, and C. arenatus. The results are consistent with the known presence of specific α-conopeptides in these species targeting nAChRs. Venom from C. coronatus, C. ebraeus, C. rattus, C. lividus, and C. miles, although purported to contained numerous conopeptides belonging to a variety of pharmacological classes, were either inactive on the preparation or caused only a minor potentiation of the twitch response. Although the ConoServer database provides valuable global data on conopeptide structure, occurrence and properties, it lacks specific information on receptor targets and affinities.

Steroidal Ammonium Compounds as New Neuromuscular Blocking Agents.

Neuromuscular blocking agents are widely used as an anesthesia auxiliary in surgery, which induce relaxation of skeletal muscles by blocking signal transmission at the neuromuscular junction. Many neuromuscular blocking agents s were developed over the past decades, but none of them fully meets the needs of the clinic by various reasons. In this study, a series of quaternary ammonium steroidal neuromuscular blocking agents were synthesized and evaluated on isolated mouse phrenic nerve-hemidiaphragms for their bioactivities. The initial separation of mono- and bis-quaternary ammonium compounds turned out to be very challenging on regular silica gel chromatography. Therefore, a facile purification method, in which the silica gel was pretreated with methanolic sodium bromide solution, was finally achieved. Compounds 3g (0.36 μm) and 4g (0.37 μm) exhibited excellent neuromuscular blocking activities, which were about sixfold to sevenfold higher in potency than that of rocuronium (2.50 μm). In addition, other bis-quaternized compounds also showed good potencies close to that of rocuronium. Furthermore, the preliminary structure-activity relationship of this series was also elucidated. Benzyl group was found to be a promising quaternary group in this series.

Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab')2 and whole IgG antivenoms.

The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21°C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20min at 21°C, and antivenom added and temperature increased to 37°C, neutralization was achieved only when the toxin was incubated for 5 or 10min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab')2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization.

Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity.

μ-Conotoxins block voltage-gated sodium channels (VGSCs) and compete with tetrodotoxin for binding to the sodium conductance pore. Early efforts identified µ-conotoxins that preferentially blocked the skeletal muscle subtype (NaV1.4). However, the last decade witnessed a significant increase in the number of µ-conotoxins and the range of VGSC subtypes inhibited (NaV1.2, NaV1.3 or NaV1.7). Twenty µ-conotoxin sequences have been identified to date and structure-activity relationship studies of several of these identified key residues responsible for interactions with VGSC subtypes. Efforts to engineer-in subtype specificity are driven by in vivo analgesic and neuromuscular blocking activities. This review summarizes structural and pharmacological studies of µ-conotoxins, which show promise for development of selective blockers of NaV1.2, and perhaps also NaV1.1,1.3 or 1.7.

Semisynthetic analogues of toxiferine I and their pharmacological properties at α7 nAChRs, muscle-type nAChRs, and the allosteric binding site of muscarinic M2 receptors.

A new series of analogues of the calabash curare alkaloid toxiferine I was prepared and pharmacologically evaluated at α7 and muscle-type nAChRs and the allosteric site of muscarinic M2 receptors. The new ligands differ from toxiferine I by the absence of one (2a–c) or two (3a–c) hydroxy groups, saturation of the exocyclic double bonds, and various N-substituents (methyl, allyl, 4-nitrobenzyl). At the muscle-type nAChRs, most ligands showed similar binding to the muscle relaxant alcuronium, indicating neuromuscular blocking activity, with the nonhydroxylated analogues 3b (Ki = 75 nM) and 3c (Ki = 82 nM) displaying the highest affinity. At α7 nAChRs, all ligands showed a moderate to low antagonistic effect, suggesting that the alcoholic functions are not necessary for antagonistic action. Compound 3c exerted the highest preference for the muscle-type nAChRs (Ki = 82 nM) over α7 (IC50 = 21 μM). As for the allosteric site of M2 receptors, binding was found to be dependent on N-substitution rather than on the nature of the side chains. The most potent ligands were the N-allyl analogues 2b and 3b (EC0.5,diss = 12 and 36 nM) and the N-nitrobenzyl derivatives 2c and 3c (EC0.5,diss = 32 and 49 nM). The present findings should help delineate the structural requirements for activity at different types of AChRs and for the design of novel selective ligands.

In vitro labelling of muscle type nicotinic receptors using a fluorophore-conjugated pinnatoxin F derivative

Fluorescent molecules are regularly utilised to study ligand–receptor interactions. Many ligands for nicotinic receptors have been conjugated with fluorophores to study receptor kinetics, recycling and ligand binding characteristics. These include small agonist molecules, as well as large peptidic antagonists. However, no small molecule antagonists have been investigated using this method. Pinnatoxin F is a newly discovered non-peptidic muscle type nicotinic receptor antagonist produced by the marine dinoflagellate species Vulcanodinium rugosum. This molecule has the potential for conjugation to a fluorophore, allowing subsequent visualisation of interactions with nicotinic receptors. Pinnatoxin F was modified by addition of diaminopolyether spacers, to which a fluorophore (VivoTag® 645) was conjugated. The fluorescent pinnatoxin was then applied to muscle sections from thy1-YFP-H transgenic mice, which express YFP in motor nerves, to allow direct visualization of fluorescent binding at the neuromuscular junction. The addition of both the diaminopolyether spacer and the VivoTag® 645 reduced the potency of pinnatoxin F, as evidenced by a reduction in in vitro neuromuscular blocking activity and in vivo toxicity. Despite this reduced potency, the fluorescent molecule selectively labelled endplate regions in thy1-YFP mouse muscle sections and this labelling was inhibited by pre-exposure of muscle sections to native pinnatoxin F or the nicotinic antagonist α-bungarotoxin. This study proves nicotinic receptor binding activity of pinnatoxin F and is the first example of a fluorophore-conjugated small-molecule antagonist for nicotinic receptors. These results indicate the potential for other small-molecule nicotinic receptor antagonists to be fluorescently labelled and used as probes for specific nicotinic receptor subtypes.

The effect of long-term oral dantrolene on the neuromuscular action of rocuronium: a case report

Oral dantrolene causes a dose-dependent depression of skeletal muscle contractility. A 52-year-old man treated with oral dantrolene for spasticity after spinal cord injury was scheduled to undergo irrigation and drainage of a thigh abscess under general anesthesia. He had taken 50 mg oral dantrolene per day for 3 years. Under standard neuromuscular monitoring, anesthesia was performed with propofol, rocuronium, and sevoflurane. A bolus dose of ED95 (0.3 mg/kg) of rocuronium could not depress T1 up to 95%. An additional dose of rocuronium depressed T1 completely and decreased the train-of-four (TOF) count to zero. There was no apparent prolongation of the neuromuscular blocking action of rocuronium. The TOF ratio was recovered to more than 0.9 within 40 minutes after the last dose of rocuronium. A small dose of oral dantrolene does not prolong the duration of action and recovery of rocuronium.

Neuromuscular blocking activity of pinnatoxins E, F and G

Pinnatoxins are produced by dinoflagellates and belong to the cyclic imine family of toxins. They are fast-acting and highly toxic when administered in vivo in rodent bioassays, causing death by respiratory depression within minutes. Studies have revealed that some cyclic imine toxins cause their toxicity by antagonizing both muscle type and heteromeric and homomeric neuronal nicotinic acetylcholine receptors (nAChRs). Pinnatoxins E, F and G all display potent toxicity in in vivo bioassays, with symptoms of toxicity similar to other cyclic imine toxins. However, very little work has been done on the mechanism of action of these pinnatoxin isomers. Thus the aim of the current study was to investigate the rank order of potency and mechanism of action of pinnatoxins E, F and G. The effects of pinnatoxin E, F and G on in vitro rat hemidiaphragm preparations were investigated using twitch tension and electrophysiological techniques to determine the effects of these toxins on cholinergic transmission at the neuromuscular junction. Pinnatoxins E, F and G all produced concentration-dependent reductions in the nerve evoked twitch response of the rat hemidiaphragm, with IC50 values ranging from 11 to 53 nM and a rank order of potency of F > G > E. Only complete washout of pinnatoxin E was evident, with pinnatoxins F and G displaying slow and incomplete washout profiles. Pinnatoxins F and G also reduced the amplitudes of spontaneous miniature endplate potentials and evoked endplate potentials at the neuromuscular junction, without affecting miniature endplate potential frequency or the resting membrane potential of the muscle fibres. These results show that pinnatoxins E, F and G are all potent neuromuscular blocking agents and cause toxicity by acting as antagonists at muscle type nicotinic acetylcholine receptors.

Neuromuscular blocking properties of tobramycin, dibekacin and ribostamycin in man (author's transl)

Neuromuscular blocking properties of tobramycin (Tobracin 60mg), dibekacin (Panmycin 100 mg) and ribostamycin (Vistamycin 1g) were studied in man during anesthesia and surgery by observing the effects of these antibiotics on muscle twitch tension. These antibiotics alone did not show any neuromuscular blocking action in the therapeutic doses. The neuromuscular blocking action of d-tubocurarine chloride was potentiated by the intravenous administration of 1g of ribostamycin. Tobramycin 60mg did not show remarkable effect, but dibekacin 100mg produced a slight potentiating effect on the action of d-tubocurarine. The enhancement of the action of d-tubocurarine was anatagonized by edrophonium and calcium. The action of succinylcholine chloride was not affected by tobramycin or ribostamycin, but it was potentiated transitorily by dibekacin. It is advisable to pay attention to possible respiratory depression when ribostamycin and dibekacin and used in combination with non-depolarizing muscle relaxants and/or anesthetics.

Sugammadex as a reversal agent for neuromuscular block: an evidence-based review.

Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the “gold standard” muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing.