Slow-acting neurotransmitters

Type II neurotransmitters These are slow-acting neurotransmitters, including acetylcholine, noradrenaline, adrenaline, dopamine and 5-hydroxytryptamine (Figure 14.6). 

Perhaps the most prominent and well-studied class of synthetic poisons are so-called cholinesterase inhibitors. Cholinesterases are important enzymes that act on compounds involved in nerve impulse transmission - the neurotransmitters (see the later section on neurotoxicity for more details). A compound called acetylcholine is one such neurotransmitter, and its concentration at certain junctions in the nervous system, and between the nervous system and the muscles, is controlled by the enzyme acetylcholinesterase the enzyme causes its conversion, by hydrolysis, to inactive products. Any chemical that can interact with acetylcholinesterase and inhibit its enzymatic activity can cause the level of acetylcholine at these critical junctions to increase, and lead to excessive neurological stimulation at these cholinergic junctions. Typical early symptoms of cholinergic poisoning are bradycardia (slowing of heart rate), diarrhea, excessive urination, lacrimation, and salivation (all symptoms of an effect on the parasympathetic nervous system). When overstimulation occurs at the so-called neuromuscular junctions the results are tremors and, at sufficiently high doses, paralysis and death. 

Histamine, an important mediator (local signaling substance) and neurotransmitter, is mainly stored in tissue mast cells and basophilic granulocytes in the blood. It is involved in inflammatory and allergic reactions. Histamine liberators such as tissue hormones, type E immunoglobulins (see p. 300), and drugs can release it. Histamine acts via various types of receptor. Binding to Hi receptors promotes contraction of smooth muscle in the bronchia, and dilates the capillary vessels and increases their permeability. Via H2 receptors, histamine slows down the heart rate and promotes the formation of HCl in the gastric mucosa. In the brain, histamine acts as a neurotransmitter. 

L E. The principal neurotransmitter released from preganglionic nerve terminals in all autonomic ganglia is acetylcholine. It acts on the postganglionic cell body to activate a nicotinic-cholinergic receptor resulting in a fast EPSP. Dopamine or norepinephrine or both are the mediators released from SIF cells or intemeurons. Neuropeptide Y is a peptide neurotransmitter. Angiotensin and serotonin are modulatory mediators. These last three contribute to the late very slow EPSP. 

It is phenyltriazine compound, chemically unrelated to existing antiepileptic drugs. It acts primarily via a dose dependent blockade of voltage sensitive sodium channels in their slow inactivated state, thus stabilizing the presynaptic neuronal membrane inhibiting release of excitatory neurotransmitters mainly glutamate. 

The biotransformation of PCP is oxidative and slow. It is believed that the oxidized product may be involved in covalent interactions with proteins resulting in the blocking of potassium channels and premature release of neurotransmitters. Another mechanistic possibility relates its structural similarities to NE, Ach and 5-HT. They have led researchers to believe that its mechanism of action may involve impaired NE reuptake and/or MAO inhibition and/or Achase inhibition and/or acting as an antimuscarinic. 

Other neurotransmitters such as serotonin and norepinephrine act as slow neurotransmitters. True or False. 

Information transfer between two neurons or between neurons and effector cells involves the release of chemical substances, which then act on the target cell by binding to appropriate receptors embedded in the plasma membrane. This process, as originally described by Otto Loewi (Loewi 1921), is termed chemical neurotransmission and occurs at contact sites known as synapses. Neurotransmitters exert their effects via members of two major families of receptors ionotropic and metabotropic neurotransmitter receptors. Activation of ionotropic receptors leads to an increase in the ion conductance of the membrane within a time scale of milliseconds or even less, whereas activation of metabotropic receptors results in slow effects (within seconds or even minutes) which involve more or less complex signaling cascades. Accordingly, information transfer via ionotropic receptors is called fast synaptic transmission, whereas the slow counterpart is called neuromodulation (Kaczmarek and Levitan 1987). 

Cocaine acts as a potent local anesthetic and is a strong CNS stimulant it extends and intensifies the effects of dopamine, norepinephrine, serotonin neurotransmitters [3], The effects of cocaine can vary in relation to the individual characteristics, the administered dose, frequency of use, and route of administration. The intranasal administration causes plasma peak concentrations after 5-20 min, the euphoric effect in 15-20 min with a half-life of 40 min. The oral route involves a slow and low absorption with plasma peak concentrations after approximately 90 min and euphoric effect in 15-20 min. Intravenous plasma peak is immediate, euphoric effect occurs after 4-8 min with a half-life of about 40 min. Finally it may be administered through inhalation of combustion products or crack vapors, with great absorption speed. 

Autopsy studies on Alzheimer-afflicted brains some 40 years later showed a similar huge drop in neurotransmitter levels, but this time it was acetylcholine (ACh) in the hippocampus —which is associated with memory. Choline-esterase inhibitors, which stop the breakdown of ACh, were introduced and are presently the only symptom treatment available (Aricept, Excelon, Reminyl, Cognex). Recently, in 2004, memantine was approved as the first treatment to slow progression of Alzheimer s in mild to moderate cases. Work is ongoing to define acetylcholine-like muscarinic M-1 agonists and M-2 agonists that act on acetylcholine receptors directly. 

VIP acts as a parasympathetic neurotransmitter in its involvement in the post-synaptic control of the heart. VIP is exactly opposite in its action to that of ACh. Vagal activity, causing release of ACh, slows the heart but co-release of VIP leads to tachycardia due to VIP preferring receptors leading to an increase in adenylate cyclase and accumulation of cAMP. 

ACh acts at two different types of cholinergic receptors Muscarinic and Nicotinic receptors. Muscarinic receptors (1) bind ACh as well as other agonists (muscarine, pilocarpine, bethan-echol) and antagonists (atropine, scopolamine). There are at least 5 different types of muscarinic receptors (M1-M5) and all have slow response times. They are coupled to G-proteins and a variety of second messenger systems. When activated, the final effect can be an opening or closing of channels for K", Ca ", or Cl . Presynaptic cholinergic receptors are of the muscarinic or nicotinic type and can modulate the release of several neurotransmitters. 

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