Vagomimetic effects of fingolimod: physiology and clinical implications.

Vagomimetic effects of fingolimod: physiology and clinical implications. CNS Neurosci Ther. 2014 Jun;20(6):496-502 Authors: Vanoli E, Pentimalli F, Botto G Abstract Fingolimod is a sphingosine 1-phosphate (S1P) receptor modulator approved to treat relapsing-remitting multiple sclerosis (MS). Initiation of treatment with fingolimod has been found to produce transient bradycardia and/or slowing of atrioventricular impulse conduction in a small proportion of patients. This effect is thought to be due to the interaction of fingolimod with S1P receptors on the surface membrane of atrial myocytes causing a vagomimetic effect, similar to the action of acetylcholine on muscarinic receptors. As a precaution, patients are under electrocardiogram (ECG) monitoring for 6 h after receiving their first dose. Fingolimod is contraindicated in patients with overt or concealed cardiac diseases. However, the Fingolimod Initiation and caRdiac Safety Trial (FIRST), which was designed specifically to investigate the cardiac profile of fingolimod, did not show an increased risk of clinically relevant cardiac events with fingolimod. This review examines the electrophysiology and pathophysiology of cardiac impulse formation in the context of fingolimod. It concludes that these vagomimetic effects should be considered benign and should not prevent the effective use of fingolimod in the treatment of patients with MS. PMID: 24836740 [PubMed - in process]
Source: CNS Neuroscience and Therapeutics - Category: Neuroscience Authors: Tags: CNS Neurosci Ther Source Type: research

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Source: Frontiers in Neurology - Category: Neurology Source Type: research
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Source: SharpBrains - Category: Neuroscience Authors: Tags: Uncategorized Brain-health Brain-Imaging digital phenotyping Mental-Health mental-illness thermometer Source Type: blogs
Publication date: Available online 10 November 2018Source: Multiple Sclerosis and Related DisordersAuthor(s): Duygu Kocyigit, Muhammed U Yalcin, Kadri M Gurses, Lale Tokgozoglu, Rana KarabudakAbstractBACKGROUNDFingolimod, a sphingosine-1-phosphate (S1P) receptor agonist, is used for treatment of relapsing-remitting multiple sclerosis (RRMS). S1P receptors that fingolimod acts upon have also been shown to be expressed on atrial myocytes. This expression pattern has been linked with the drug's cardiovascular effects, such as bradycardia. We aimed to evaluate the clinical and electrocardiographic predictors of heart rate (HR)...
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Conclusions The results, using techniques novel to MS investigation, showed diminished baroreceptor reflex and impaired sympathetic function using frequency domain systolic blood pressure variability analysis.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Conclusions Deterioration of cardiac autonomic regulation during the disease course associates with disabling but not with benign RRMS. Our findings suggest that assessment of cardiac autonomic regulation should be included in the evaluation of RRMS disease course. In addition, patients with disabling RRMS might be prone to unfavorable cardiovascular outcome also due to deterioration of autonomic nervous system.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Electrocardiographic artifacts are defined as electrocardiographic alterations, not related to cardiac electrical activity. As a result of artifacts, the components of the electrocardiogram (ECG) such as the baseline and waves can be distorted. Motion artifacts are due to shaking with rhythmic movement. Examples of motion artifacts include tremors with no evident cause, Parkinson’s disease, cerebellar or intention tremor, anxiety, hyperthyroidism, multiple sclerosis, and drugs such as amphetamines, xanthines, lithium, benzodiazepines, or shivering (due to hypothermia, fever (rigor due to shaking), cardiopulmonary res...
Source: Annals of Noninvasive Electrocardiology - Category: Cardiology Authors: Tags: REVIEW ARTICLE Source Type: research
ConclusionsCardiac repolarization prolonged and heart rate increased during the disease course in RRMS patients with motor but not with sensory onset symptom. This suggests different traits in RRMS according to its initial manifestation and also association of motor onset symptom with more unfavorable cardiovascular prognostic determinants. Multiple sclerosis is associated with prolonged cardiac repolarization but the underlying physiology has remained unknown. In this study, cardiac repolarization was found to prolong and heart rate increase during the disease course in RRMS patients with motor but not with sensory onset...
Source: Brain and Behavior - Category: Neurology Authors: Tags: ORIGINAL RESEARCH Source Type: research
This study was aiming to further elucidate the effects of fingolimod on cardiac electrophysiology at three different levels: (i) in vitro, (ii) ex vivo, and (iii) in vivo. (i) Patch‐clamp experiments in whole cell configuration were performed on Cav1.2‐transfected tsA201 cells exposed to fingolimod‐phosphate 100 or 500 nmol/L (n = 27 cells, total) to measure drug effect on L‐type calcium current (ICaL). (ii) Langendorff perfusion experiments were undertaken on male Hartley guinea‐pigs isolated hearts (n = 4) exposed to fingolimod 10 and 100 nmol/L to evaluate drug‐induced effects on monophasic action potential ...
Source: Fundamental and Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research
Conclusions:Results from this long-term study over a period of 96 weeks will provide valuable information regarding the safety and tolerability of ALKS 8700 (462 mg twice daily) in patients with RRMS.Study Supported by:This study is sponsored by Alkermes, Inc., Waltham, MA, USA.Disclosure: Dr. Naismith has received personal compensation for activities with Acorda, Alkermes, Bayer, Biogen, EMD Serono, Genentech, Genyzme, Novartis, and Teva. Dr. Naismith has received research support from Alkermes. Dr. Leigh-Pemberton has received personal compensation for activities with Alkermes, Inc. as an employee. Dr. Claxton has receiv...
Source: Neurology - Category: Neurology Authors: Tags: MS and CNS Inflammatory Disease Poster Discussion Session Source Type: research
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Source: Fundamental and Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research
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