Postsynaptic inhibition

The best-understood sites of action of morphine are at spinal and brainstem/ midbrain loci, producing both the wanted and unwanted effects of the opioid. The spinal actions of opioids and their mechanisms of analgesia involve (1) reduced transmitter release from nociceptive C-fibres so that spinal neurons are less excited by incoming painful messages, and (2) postsynaptic inhibitions of neurons conveying information from the spinal cord to the brain. This dual action of opioids can result in a... 

Ammonia has deleterious effects on brain function by direct and indirect mechanisms. Concentrations of ammonia in the 1-2 mmol/1 range, equivalent to those reported in the brain in liver failure, impair postsynaptic inhibition in cerebral cortex and brainstem by a direct effect on Cl extrusion from the postsynaptic neuron. Millimolar concentrations of ammonia also inhibit excitatory neurotransmission. Synaptic transmission from Schaffer collaterals to CA1 hippocampal neurons is reversibly depressed by 1 mmol/1 ammonia, and the firing of CA1 neurons by iontophoretic application of glutamate is inhibited by 2 mmol/1 ammonia [10],... 

Sigma 2000 MVIIA/postsynaptic inhibition or blocking of Neurex (Elan nicotinic acetylcholine receptor, according to type Pharm.) Kohno 1995, and its synthetic version SNX-111... 

GABA Supraspinal and spinal interneurons involved in pre-and postsynaptic inhibition GABAa muscimol Bicuculline, picrotoxin Inhibitory t CPconductance... 

Baclofen GABAb agonist, facilitates spinal inhibition of motor neurons Pre- and postsynaptic inhibition of motor output Severe spasticity due to cerebral palsy, mulitple sclerosis, stroke Oral, intrathecal Toxicities Sedation, weakness... 

Tizanidine o -Adrenoceptor agonist in the spinal cord Presynaptic and postsynaptic inhibition of reflex motor output Spasm due to multiple sclerosis, stroke, amyotrophic lateral sclerosis Renal and hepatic elimination t duration, 3-6 h Toxicities Weakness, sedation hypotension... 

As a result of these actions opioids inhibit neurotransmission at the presynaptic and postsynaptic sites. Presynaptic inhibition depends mostly on the direct inhibitory effect on transmitter exocytosis from membrane-associated storage vessels. This direct effect is increased by the inhibition of Ca2+ channels, since Ca2+ ions trigger the transmitter release. Activation of K+ ions induces membrane hyperpolarization which is the most important action component of postsynaptic inhibition. 

Giesler, G. J., Gerhart, K. D., Yezierski, R. P., Wilcox, T. K., Willis, W. D. Postsynaptic inhibition of primate spinothalamic neurons by stimulation in nucleus raphe magnus, Brain Res. 1981, 204, 184-188. 

Tizanidine (Zanaflex) is classified as an alpha-2 adrenergic agonist, meaning that this drug binds selectively to the alpha-2 receptors in the CNS and stimulates them. Alpha-2 receptors are found at various locations in the brain and spinal cord, including the presynaptic and postsynaptic membranes of spinal interneurons that control alpha motor neuron excitability. Stimulation of these alpha-2 receptors inhibits the firing of interneurons that relay information to the alpha motor neuron that is, interneurons that comprise polysynaptic reflex arcs within the spinal cord.27 Tizanidine appears to bind to receptors on spinal interneurons, decrease the release of excitatory neurotransmitters from their presynaptic terminals (presynaptic inhibition), and decrease the excitability of the postsynaptic neuron (postsynaptic inhibition).40 Inhibition of spinal interneurons results in decreased excitatory input onto the alpha motor neuron, with a subsequent decrease in spasticity of the skeletal muscle supplied by that neuron. 

Yanovsky Y, Mades S, Misgeld U (2003) Retrograde signaling changes the venue of postsynaptic inhibition in rat substantia nigra. Neurosci 122 317-238... 

Fozard JR, Ali AT (1978) Receptors for 5-hydroxytryptamine on the sympathetic nerves of the rabbit heart. Naunyn Schmiedeberg s Arch Pharmacol 301 223-35 Frank K, Fuortes MGF (1957) Presynaptic and postsynaptic inhibition of neurosynaptic reflex. Fed Proc 16 39 40... 

Shin RM, Masuda M, Masami M, Sano H, Shirasawa T, Song WJ, Kobayashi K, Aosaki T (2003) Dopamine D4 receptor-induced postsynaptic inhibition of GABAergic currents in mouse globus pallidus neurons. J Neurosci 23 11662-11672... 

Curtis DR. The pharmacology of spinal postsynaptic inhibition. Prog Brain Res 1969 31 171-89. 

The toxic and therapeutic effects of this drug have been attributed, in large part, to the potentiation of y-aminobutyric acid (GABA) in the central nervous system (CNS). GABA is a neurotransmitter which mediates pre- and postsynaptic inhibition. Diazepam influences GABA activity by binding to the benzodiazepine receptor complex, thus resulting in increased CNS inhibition. 

K- and 5-opioid receptors a2-adrenoceptors somatostatin receptors). It should be noted that the G-protein seems to couple either to open the K -channel or to close a Ca -channel. according to tissue-dependent factors this seems to be the major mechanism of both presynaptic and postsynaptic inhibition. Clinically, opioid analgesics such as morphine, and sympathetic neuron inhibitors such as clonidine, appear to work by this mechanism. 

The CeA contains neurons that respond differentially to hedonically positive and negative taste stimuli (Nishijo et al., 1998) and both the CeA and basolateral amygdala are involved in conditioned taste aversion learning (Yamamoto et al., 1994). Extracellular action potentials were recorded from 109 taste-responsive cells in the NST and analyzed for a change in excitability following electrical and chemical stimulation of the CeA (Li et ak, 2002). An orthodromic excitatory response was observed in 33 of 109 taste-responsive cells (30.3%). An initial decrease in excitability, suggestive of postsynaptic inhibition, was observed in 3 of the... 

Andersen P, Eccles JC, Voorhoeve PE (1964) Postsynaptic inhibition of cerebellar Purkinje cells. J Neurophysiol 27 1138-1153. 

Obata K, Ito M, Ochi R, Sato N (1967) Pharmacological properties of the postsynaptic inhibition by Purkinje cell axons and the action of gamma-aminobutyric acid on Deiter s neurones. Exp. Brain Res.. 4, 4i-51. 

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