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Related Concept Videos

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
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GPCRs Regulate Adenylyl Cylase Activity01:09

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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Antianginal Drugs: Calcium Channel Blockers and Ranolazine01:25

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Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
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Pharmacogenomics: Identification of New Drug Targets01:29

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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers01:27

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β-receptor blockers significantly impact the cardiovascular system by counteracting catecholamine-induced sympathetic responses. These medications decrease heart rate, contractility, and cardiac output, potentially leading to cardiac depression, life-threatening bradycardia, and death. Therapeutically, β-blockers function as mild antihypertensives and are utilized in treating angina pectoris and cardiac arrhythmias. However, nonselective β-blockers inhibit β2-receptors in...
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Ex Vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents
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Wiping Out CGRP: Potential Cardiovascular Risks.

Antoinette MaassenVanDenBrink1, Joris Meijer2, Carlos M Villalón3

  • 1Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

Trends in Pharmacological Sciences
|June 25, 2016
PubMed
Summary
This summary is machine-generated.

New migraine drugs targeting calcitonin gene-related peptide (CGRP) show promise but may increase risks of stroke and heart attack. Further studies are needed to assess these potential cardiovascular and cerebrovascular safety issues.

Keywords:
CGRPantibodycardiac ischemiacerebral ischemiamigraine

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Cardiology

Background:

  • Migraine is a prevalent neurovascular disorder linked to a higher risk of cardio- and cerebrovascular ischemia.
  • The trigeminovascular system activation and calcitonin gene-related peptide (CGRP) release are implicated in migraine pathophysiology.
  • CGRP plays a role as a vasodilatory safeguard during ischemic events in the brain and heart.

Purpose of the Study:

  • To review potential cerebro- and cardiovascular risks associated with CGRP pathway blockade for migraine prevention.
  • To identify necessary clinical and preclinical studies for assessing the safety of CGRP-targeting migraine therapies.

Main Methods:

  • Review of existing clinical and preclinical studies on CGRP's role in migraine and ischemia.
  • Analysis of the potential impact of CGRP blockade on ischemic events.

Main Results:

  • Monoclonal antibodies targeting CGRP or its receptor are under investigation for migraine prevention with promising preliminary efficacy.
  • CGRP blockade might convert transient ischemic events into severe infarcts due to its vasodilatory protective function.

Conclusions:

  • While CGRP antagonists show potential for migraine treatment, their safety regarding cardiovascular and cerebrovascular risks requires thorough investigation.
  • Further research, including clinical and preclinical studies, is essential to evaluate the safety profile of CGRP-targeting drugs.