Hi everybody, first of all I would like to sincerely apologize for the delay in putting up my blog for this month as I was a bit busy with my academic schedule. Here this time I would like to discuss briefly about Glutamatergic neurotransmission which is one of the key neurotransmission pathways involved in functioning of brain. It plays an important role in learning and memory. All parts of the CNS are supplied with Glutamatergic Synapses. Binding of glutamate to its receptors elicits numerous responses at molecular and cellular level that mediate many physiologic and pathophysiologic pathways including, -Hyperalgesia -Cerebral neurotoxicity -Synaptic changes involved in memory formation GLUTAMATE RECEPTORS:- The receptors to which glutamate binds are broadly classified into Two Categories Ionotropic glutamate receptors: - -These are AMPA, Kainate & NMDA. -Mediate fast excitatory synaptic responses -Multi-subunit cation selective channels -Causes Na+, K+, and Ca2+ ions across plasma membrane. Metabotropic glutamate receptors (mGluR): - These are GPCR's whish are further divide into three groups I, II, & III. Group I causes neuronal excitation either by Phospholipase C activation and IP3 mediated intracellular Ca2+ release or through adenylyl cyclase activation and cAMP generation. Group II & III receptors inhibit adenylyl cyclase and decrease cAMP production. GLUTAMATE- FUNCTIONAL ROLE: The fast synaptic transmission mediated by AMPA receptors, and in certain regions by Kainate receptors mediate fast synaptic excitatory transmission in the CNS which is fundamental for our brains to function. -AMPA receptors are present on astrocytes and also on neurons, and these cells play an important role in communication in brain. -The effects of Metabotropic glutamate receptors are modulatory rather than direct, involving mainly post synaptic excitatory effects and pre synaptic inhibition. -NMDA and Metabotropic receptors play a particular role in long-term adaptive and pathological changes in brain. -AMPA and Kainate receptors mainly involved in the mediation of fast excitatory transmission, which, if blocked leads to complete inactivity of brain function. These are also involved in Synaptic Plasticity (Long term changes in synaptic connectivity and efficacy either by physiological alterations in neuronal activity or resulting from pathological disturbances). -Synaptic plasticity cannot be attributed to any single mechanism, but one of the extensively studied component is Long Term Potentiation (LTP). -It can be best described as the enhanced activity of the synaptic transmission that occurs at various CNS synapses initiated by a short burst of high frequency stimulation from pre-synaptic terminals. -If the stimulation from pre-synaptic terminals is by low frequency long chain of stimulus, it develops into Long-term depression. These phenomenons are mainly implicated in neurodegenerative disorders such as Alzheimer's, and in damage of brain due to stroke and head injury. -Many of the available therapeutic medications are antagonists at the glutamate receptors and are aimed at reducing the firing of the neurons and also blocking of stimulus thus reducing the brain damage. DRUGS: Antagonists at- NMDA:- Kyneurenic acid and 7-chloro-kyneurenic acid Channel Blockers are Dizocilpine, Phencyclidine, Ketamine, and Memantine AMPA:- NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzoquinoxaline), CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) (These are experimental tools only, not useful therapeutically) KAINATE:- NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzoquinoxaline) METABOTROPIC:- MCPG (a-methyl-4-carboxyphenylglycine) Agonists- Among the agonists primary focus is on the AMPA receptor modulators which act by reducing receptor desensitization and improve cognitive performance and memory. E.g. Cyclothiazide, Piracetam, Aniracetam. Reference: Rang and Dale PHARMACOLOGY, 6th Edition, Elsevier Publications, Pg: 480-487. "THIS BLOG IS FREE OF PLAGIARISED MATERIAL"