Nimodipine
Nicotinic Acids
Calcium Channel Blockers
Vasospasm, Intracranial
Brain Ischemia
Dihydropyridines
Subarachnoid Hemorrhage
Flunarizine
Calcium Channels, L-Type
Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. (1/430)
The D3 dopamine receptor is postulated to play an important role in the regulation of neurotransmitter secretion at both pre- and postsynaptic terminals. However, this hypothesis and the underlying mechanisms remain untested because of the lack of D3-selective ligands, paucity of appropriate model secretory systems, and the weak and inconsistent coupling of D3 receptors to classical signal transduction pathways. The absence of ligands that selectively discriminate between D3 and D2 receptors in vivo precludes the study of D3 receptor function in the brain and necessitates the use of heterologous expression systems. In this report we demonstrate that activation of the human D3 dopamine receptor expressed in the AtT-20 neuroendocrine cell line causes robust inhibition of P/Q-type calcium channels via pertussis toxin-sensitive G-proteins. In addition, using the vesicle trafficking dye FM1-43, we show that D3 receptor activation significantly inhibits spontaneous secretory activity in these cells. Our results not only support the hypothesis that the D3 receptor can regulate secretory activity but also provide insight into the underlying signaling mechanisms. We propose a functional model in which the D3 receptor tightly regulates neurotransmitter release at a synapse by only allowing the propagation of spikes above a certain frequency or burst-duration threshold. (+info)L-type Ca2+ channels and K+ channels specifically modulate the frequency and amplitude of spontaneous Ca2+ oscillations and have distinct roles in prolactin release in GH3 cells. (2/430)
GH3 cells showed spontaneous rhythmic oscillations in intracellular calcium concentration ([Ca2+]i) and spontaneous prolactin release. The L-type Ca2+ channel inhibitor nimodipine reduced the frequency of Ca2+ oscillations at lower concentrations (100nM-1 microM), whereas at higher concentrations (10 microM), it completely abolished them. Ca2+ oscillations persisted following exposure to thapsigargin, indicating that inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ stores were not required for spontaneous activity. The K+ channel inhibitors Ba2+, Cs+, and tetraethylammonium (TEA) had distinct effects on different K+ currents, as well as on Ca2+ oscillations and prolactin release. Cs+ inhibited the inward rectifier K+ current (KIR) and increased the frequency of Ca2+ oscillations. TEA inhibited outward K+ currents activated at voltages above -40 mV (grouped within the category of Ca2+ and voltage-activated currents, KCa,V) and increased the amplitude of Ca2+ oscillations. Ba2+ inhibited both KIR and KCa,V and increased both the amplitude and the frequency of Ca2+ oscillations. Prolactin release was increased by Ba2+ and Cs+ but not by TEA. These results indicate that L-type Ca2+ channels and KIR channels modulate the frequency of Ca2+ oscillations and prolactin release, whereas TEA-sensitive KCa,V channels modulate the amplitude of Ca2+ oscillations without altering prolactin release. Differential regulation of these channels can produce frequency or amplitude modulation of calcium signaling that stimulates specific pituitary cell functions. (+info)Effect of saponins of Panax notoginseng on synaptosomal 45Ca uptake. (3/430)
AIM: To explore the calcium uptake antagonism of saponins of Panax notoginseng (PNS). METHODS: Synaptosomes were prepared from rat cerebral cortex by using differential Ficoll gradients. The effects of PNS on synaptosomal 45Ca uptake were measured in vitro or after acute treatment. RESULTS: PNS 50-800 mg.L-1 produced a concentration-rated inhibition of Ca2+ uptake [IC50 = 111 (46-176) mg.L-1]. Both initial and maximal uptake were inhibited. Similar effect was obtained after acute PNS treatment with 200 mg.kg-1 i.p. The blocking effect of PNS was reversed by calcium in media. CONCLUSION: PNS is a calcium channel blocker in neurons. (+info)The effect and management of delayed vasospasm after aneurysmal subarachnoid hemorrhage. (4/430)
Delayed cerebral vasospasm after aneurysm rupture is one of the major complications of subarachnoid hemorrhage. The purpose of this review was to determine the true incidence of vasospasm. All literature on cerebral aneurysms from 1960 onwards was reviewed, and the figures extracted from publications that mentioned vasospasm. Angiographic vasospasm, where patients were studied at the time of peak incidence, was reported in about two thirds of cases. Symptomatic vasospasm or delayed ischemia affects about one third. Untreated, nearly a third of those with ischemic deficits die and a similar proportion are left permanently disabled. Variations of Triple-H (hypervolemia, hypertension, hemodilution) therapy, used early after hemorrhage for prophylaxis of vasospasm, are associated with a decrease of nearly half in the incidence of delayed ischemia. When used as therapy outcome also appears better, with a reduction particularly in the death rate. Calcium antagonists have been widely used, especially nimodipine. In several controlled trials the incidence of delayed ischemia was significantly reduced. More importantly, the overall outcome of all subarachnoid hemorrhage patients was better with nimodipine prophylaxis. The 21-aminosteroid tirilazad mesylate has been the subject of several trials. In one the overall outcome of all patients was improved, but the effect was essentially in males only. Further studies with larger doses in females are being analyzed. (+info)Effects of dl-3-n-butylphthalide on regional cerebral blood flow in right middle cerebral artery occlusion rats. (5/430)
AIM: To study the effect of dl-3-n-butylphthalide (NBP) on regional cerebral blood flow (rCBF) in forcal cerebral ischemia rats. METHODS: In chloral hydrate-anesthetized rat, the proximal portion of right middle cerebral artery (RMCA) was occluded, and H2 needle electrode was implanted in right striatum. rCBF was monitored in striatum using hydrogen clearance method. RESULTS: Ten min after RMCA occlusion (RMCAO), NBP (5, 10, 20 mg.kg-1 i.p.) markedly increased rCBF to striatum (P < 0.01). When NBP was given i.p. 40 min after RMCAO, the increasing effect on rCBF was also observed (P < 0.05). However, when NBP was injected i.p. 60 min after RMCAO, the increasing effect of NBP on rCBF was not found. In NBP-pretreated (i.p. 40 min before RMCAO) group, rCBF in striatum measured at different time points of 30, 60, 90, 120, 150, and 180 min after RMCAO were increased by 97%, 107%, 136%, 211%, 173%, and 317%, respectively, compared with the percentages of vehicle group. The potency of the effect of Nim (0.5 mg.kg-1 i.p.) was similar to that of NBP (10 mg.kg-1 i.p.). CONCLUSION: NBP pre-treatment or post-treatment markedly enhanced the rCBF to striatum in RMCAO rats. (+info)Inhibitory effects of nimodipine on platelet aggregation and thrombosis. (6/430)
AIM: To study the inhibitory effects of nimodipine (Nim) on rat platelet aggregation and arterial thrombosis in vivo. METHODS: The aggregation rate of platelets induced by ADP and inhibition rate of Nim were measured by the change of light transmission. Effect of Nim on arterial occlusion time was measured by electric stimulation. Effect of Nim on the contents of 6-keto-PGF1 alpha and TXB2 in serum was measured by radioimmunoassay. RESULTS: Nim 4.5, 9, 18, and 36 mg.kg-1.d-1 ig for 4 d restrained the platelet aggregation. The IC50 (95% confidence limits) was 26 (9-44) mg.kg-1. Nim 4.5, 9, and 18 mg.kg-1.d-1 ig for 4 d markedly prolonged the time of thrombotic occlusion in carotid artery induced by electric stimulation. Nim 9 and 18 mg.kg-1.d-1 improved the imbalance of 6-keto-PGF1 alpha/TXB2 in serum after thrombosis. CONCLUSION: Nim was a potent inhibitor of platelet aggregation, which was partially concerned with the improved balance of 6-keto-PGF1 alpha/TXB2. (+info)Nimodipine and perfusion changes after stroke. (7/430)
BACKGROUND AND PURPOSE: Meta-analysis of previous trials of oral nimodipine in acute stroke has suggested a benefit when commenced within 12 hours of onset. We sought to study the effect of oral nimodipine on reperfusion after acute stroke and the relation between reperfusion and outcome. METHODS: Fifty patients with acute middle cerebral artery territory cortical infarction were blindly randomized within 12 hours of onset to either oral nimodipine (30 mg every 6 hours) or placebo. Treatment was continued for 2 weeks. Cerebral blood flow was assessed with the use of 99mTc-hexamethylpropyleneamine oxime single-photon emission CT before therapy, 24 hours later, and at 3 months. Hypoperfusion was measured by a validated volumetric technique. Neurological impairment and functional outcome were assessed with the Canadian Neurological Scale and Barthel Index, respectively. Tissue loss was measured with CT at 3 months. Four patients were excluded from analysis for technical reasons. RESULTS: Twenty-three patients received nimodipine, and 23 received placebo. In the nimodipine group, there was early reperfusion that was not maintained at outcome (P=0.01). In the placebo group, mean infarct hypoperfusion volumes showed no overall change. Nonnutritional reperfusion in nimodipine-treated patients was associated with adverse neurological (P=0.05) and functional outcome (P=0.06). There was, however, no difference in clinical outcome between the 2 groups. CONCLUSIONS: Oral nimodipine administered within 12 hours enhanced acute reperfusion, but this was largely nonnutritional. Larger studies using a shorter treatment delay are required to evaluate the clinical efficacy of nimodipine in acute ischemic stroke. (+info)Studies on maitotoxin-induced intracellular Ca(2+) elevation in chinese hamster ovary cells stably transfected with cDNAs encoding for L-type Ca(2+) channel subunits. (8/430)
The aim of the present study was to characterize the role played by different L-type Ca(2+) channel subunits in [Ca(2+)](i) increase induced by maitotoxin (MTX). In the presence of 5 mM extracellular K(+), MTX (0.01-0.5 ng/ml) induced a significant concentration-dependent increase in Fura-2-monitored [Ca(2+)](i) in single Chinese hamster ovary (CHO) cells expressing the alpha(1c) (CHOCalpha9 cells) or the alpha(1c)beta(3)alpha(2)delta (CHOCalpha9beta3alpha2/delta4 cells) subunits of voltage-gated Ca(2+) channels (VGCCs), whereas the effect was much reduced in wild-type CHO cells lacking VGCCs. In addition, MTX effect on CHOCalpha9, CHOCalpha9beta3alpha2/delta4, and GH(3) cells (0.01-0.1 ng/ml) was inhibited by the selective L-type Ca(2+) channel entry-blocker nimodipine (10 microM); a nimodipine-insensitive component was still present, particularly at high (>1 ng/ml) toxin concentrations. In CHOCalpha9beta3alpha2/delta4 cells, depolarizing concentrations of extracellular K(+) (55 mM) reinforced the [Ca(2+)](i) increase induced by MTX (0.1 ng/ml), and this effect was prevented by nimodipine (10 microM). Finally, patch-clamp experiments in CHOCalpha9beta3alpha2/delta4 cells showed that low MTX concentrations (0.03 ng/ml) induced the occurrence of an inward current at -60 mV, which was completely prevented by Cd(2+) (100 microM) and by nimodipine (10 microM), whereas the same dihydropyridine concentration (10 microM) failed to prevent the electrophysiological effects of a higher toxin concentration (3 ng/ml). In conclusion, the results of the present study showed that MTX-induced [Ca(2+)](i) elevation involves two components: 1) an action on L-type VGCCs at the pore-forming alpha(1c) subunit level, which is responsible for the greatest rise of [Ca(2+)](i); and 2) a VGCC-independent mechanism that is present both in excitable and in nonexcitable cells and is responsible for a lower elevation of [Ca(2+)](i). (+info)Nimodipine is an antihypertensive and calcium channel blocker drug, which is primarily used in the prevention and treatment of neurological deficits following subarachnoid hemorrhage (SAH), a type of stroke caused by bleeding in the space surrounding the brain. It works by relaxing and dilating blood vessels in the brain, improving blood flow, and preventing spasms in cerebral arteries, which can help reduce the risk of further damage to brain tissues.
Nimodipine is available in the form of capsules or an injectable solution for medical use. It is crucial to follow a healthcare professional's instructions carefully when using this medication, as improper usage may lead to unwanted side effects or reduced effectiveness. Common side effects include headache, dizziness, nausea, and flushing.
It is essential to consult with a healthcare provider for personalized medical advice regarding the use of Nimodipine or any other medications.
Niacin, also known as nicotinic acid, is a form of vitamin B3 (B-complex vitamin) that is used by the body to turn food into energy. It is found in various foods including meat, fish, milk, eggs, green vegetables, and cereal grains. Niacin is also available as a dietary supplement and prescription medication.
As a medication, niacin is primarily used to treat high cholesterol levels. It works by reducing the production of LDL (bad) cholesterol in the body and increasing the levels of HDL (good) cholesterol. Niacin can also help lower triglycerides, another type of fat found in the blood.
Niacin is available in immediate-release, sustained-release, and extended-release forms. The immediate-release form can cause flushing of the skin, itching, tingling, and headaches, which can be uncomfortable but are not usually serious. The sustained-release and extended-release forms may have fewer side effects, but they can also increase the risk of liver damage and other serious side effects.
It is important to note that niacin should only be taken under the supervision of a healthcare provider, as it can interact with other medications and have potentially serious side effects.
Calcium channel blockers (CCBs) are a class of medications that work by inhibiting the influx of calcium ions into cardiac and smooth muscle cells. This action leads to relaxation of the muscles, particularly in the blood vessels, resulting in decreased peripheral resistance and reduced blood pressure. Calcium channel blockers also have anti-arrhythmic effects and are used in the management of various cardiovascular conditions such as hypertension, angina, and certain types of arrhythmias.
Calcium channel blockers can be further classified into two main categories based on their chemical structure: dihydropyridines (e.g., nifedipine, amlodipine) and non-dihydropyridines (e.g., verapamil, diltiazem). Dihydropyridines are more selective for vascular smooth muscle and have a greater effect on blood pressure than heart rate or conduction. Non-dihydropyridines have a more significant impact on cardiac conduction and contractility, in addition to their vasodilatory effects.
It is important to note that calcium channel blockers may interact with other medications and should be used under the guidance of a healthcare professional. Potential side effects include dizziness, headache, constipation, and peripheral edema.
Intracranial vasospasm is a medical condition characterized by the narrowing or constriction of the intracranial arteries, which are the blood vessels that supply blood to the brain. This narrowing is usually caused by the contraction or spasming of the smooth muscle in the walls of the arteries, leading to reduced blood flow and oxygen delivery to the brain tissue.
Intracranial vasospasm is often associated with subarachnoid hemorrhage (SAH), a type of stroke caused by bleeding in the space surrounding the brain. SAH can cause the release of blood components, such as hemoglobin and iron, which can irritate and damage the walls of the arteries. This irritation can trigger an inflammatory response that leads to the contraction of the smooth muscle in the artery walls, causing vasospasm.
Vasospasm can cause further ischemia (reduced blood flow) or infarction (tissue death) in the brain, leading to serious neurological deficits or even death. Therefore, prompt diagnosis and treatment of intracranial vasospasm are crucial for improving patient outcomes. Treatment options may include medications to dilate the blood vessels, angioplasty (balloon dilation) or stenting procedures to mechanically open up the arteries, or surgical intervention to relieve pressure on the brain.
Brain ischemia is the medical term used to describe a reduction or interruption of blood flow to the brain, leading to a lack of oxygen and glucose delivery to brain tissue. This can result in brain damage or death of brain cells, known as infarction. Brain ischemia can be caused by various conditions such as thrombosis (blood clot formation), embolism (obstruction of a blood vessel by a foreign material), or hypoperfusion (reduced blood flow). The severity and duration of the ischemia determine the extent of brain damage. Symptoms can range from mild, such as transient ischemic attacks (TIAs or "mini-strokes"), to severe, including paralysis, speech difficulties, loss of consciousness, and even death. Immediate medical attention is required for proper diagnosis and treatment to prevent further damage and potential long-term complications.
Cerebrovascular circulation refers to the network of blood vessels that supply oxygenated blood and nutrients to the brain tissue, and remove waste products. It includes the internal carotid arteries, vertebral arteries, circle of Willis, and the intracranial arteries that branch off from them.
The internal carotid arteries and vertebral arteries merge to form the circle of Willis, a polygonal network of vessels located at the base of the brain. The anterior cerebral artery, middle cerebral artery, posterior cerebral artery, and communicating arteries are the major vessels that branch off from the circle of Willis and supply blood to different regions of the brain.
Interruptions or abnormalities in the cerebrovascular circulation can lead to various neurological conditions such as stroke, transient ischemic attack (TIA), and vascular dementia.
Dihydropyridines are a class of compounds that contain a core structure of two fused rings, each containing six carbon atoms, with a hydrogen atom attached to each of the two central carbon atoms. They are commonly used in pharmaceuticals, particularly as calcium channel blockers in the treatment of cardiovascular diseases.
Calcium channel blockers, including dihydropyridines, work by blocking the influx of calcium ions into cardiac and vascular smooth muscle cells. This leads to relaxation of the muscles, resulting in decreased peripheral resistance and reduced blood pressure. Dihydropyridines are known for their potent vasodilatory effects and include medications such as nifedipine, amlodipine, and felodipine.
It is important to note that while dihydropyridines can be effective in treating hypertension and angina, they may also have side effects such as headache, dizziness, and peripheral edema. Additionally, they may interact with other medications, so it is essential to consult a healthcare provider before starting or changing any medication regimen.
A subarachnoid hemorrhage is a type of stroke that results from bleeding into the space surrounding the brain, specifically within the subarachnoid space which contains cerebrospinal fluid (CSF). This space is located between the arachnoid membrane and the pia mater, two of the three layers that make up the meninges, the protective covering of the brain and spinal cord.
The bleeding typically originates from a ruptured aneurysm, a weakened area in the wall of a cerebral artery, or less commonly from arteriovenous malformations (AVMs) or head trauma. The sudden influx of blood into the CSF-filled space can cause increased intracranial pressure, irritation to the brain, and vasospasms, leading to further ischemia and potential additional neurological damage.
Symptoms of a subarachnoid hemorrhage may include sudden onset of severe headache (often described as "the worst headache of my life"), neck stiffness, altered mental status, nausea, vomiting, photophobia, and focal neurological deficits. Rapid diagnosis and treatment are crucial to prevent further complications and improve the chances of recovery.
Intravenous (IV) administration is a medical procedure where medication or fluids are delivered directly into a vein. This method allows for rapid absorption and distribution of the substance throughout the body. It is commonly used to provide immediate treatment in emergency situations, administer medications that cannot be given by other routes, or deliver fluids and electrolytes when someone is dehydrated.
To perform an IV administration, a healthcare professional first prepares the necessary equipment, including a sterile needle or catheter, syringe, and the medication or fluid to be administered. The site of insertion is typically on the back of the hand, inner elbow, or forearm, where veins are more visible and accessible. After cleaning and disinfecting the skin, the healthcare professional inserts the needle or catheter into the vein, securing it in place with tape or a dressing. The medication or fluid is then slowly injected or infused through the IV line.
Possible risks associated with IV administration include infection, infiltration (when the fluid leaks into surrounding tissue instead of the vein), extravasation (when the medication leaks out of the vein and causes tissue damage), and phlebitis (inflammation of the vein). Proper technique and monitoring during and after IV administration can help minimize these risks.
Flunarizine is a medication that belongs to the class of drugs known as calcium channel blockers. It is primarily used in the prevention of migraine headaches and to treat vertigo (a spinning sensation) associated with various conditions such as Meniere's disease. Flunarizine works by blocking calcium channels, which reduces the influx of calcium ions into cells. This action leads to relaxation of smooth muscle, decreased neurotransmitter release, and inhibition of platelet aggregation, ultimately helping to prevent migraines and alleviate symptoms of vertigo. It is available in the form of tablets for oral administration.
Calcium channels, L-type, are a type of voltage-gated calcium channel that are widely expressed in many excitable cells, including cardiac and skeletal muscle cells, as well as certain neurons. These channels play a crucial role in the regulation of various cellular functions, such as excitation-contraction coupling, hormone secretion, and gene expression.
L-type calcium channels are composed of five subunits: alpha-1, alpha-2, beta, gamma, and delta. The alpha-1 subunit is the pore-forming subunit that contains the voltage sensor and the selectivity filter for calcium ions. It has four repeated domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segment in each domain functions as a voltage sensor, moving outward upon membrane depolarization to open the channel and allow calcium ions to flow into the cell.
L-type calcium channels are activated by membrane depolarization and have a relatively slow activation and inactivation time course. They are also modulated by various intracellular signaling molecules, such as protein kinases and G proteins. L-type calcium channel blockers, such as nifedipine and verapamil, are commonly used in the treatment of hypertension, angina, and certain cardiac arrhythmias.