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COLLEGE OF PHARMACY BAGALKOT KARNATAKA DOPAMINERGIC RECEPTORSTABLE OF CONTENTS: TABLE OF CONTENTS Introduction o Location and function Biosynthesis o Agonist and antagonist Transporters o Reference Dopaminergic pathways Degradation Function Pharmacological action Deficiency Receptors ClassificationPowerPoint Presentation: DOPAMINE Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England. It was named dopamine because it was a monoamine , neurotransmitter formed in the brain from the amino acid tyrosine. Its a predominant neurotransmitter in mammalian brain as it controls variety of functions like locomotor activity, cognition, emotion ,positive reinforcement, food intake & endocrine regulation. The function of dopamine as a neurotransmitter was discovered in 1958 by Arvid Carlsson and Nils-Ake Hillarp. Dopamine is most abundant in corpus striatum , high conc. Also occurs in certain part of limbic system and hypothalamus.PowerPoint Presentation: Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary. Dopaminergic neurons are present chiefly in the ventral tegmental area (VTA) of the midbrain, the substantia nigra, and the arcuate nucleus of the hypothalamus. 6-hydroxydopamine , selectively destroys dopaminergic nerve terminals. BIO SYNTHESIS OF DOPAMINE : BIO SYNTHESIS OF DOPAMINETRANSPORTERS: TRANSPORTERS VMAT-2 is responsible for packaging DA into synaptic vesicles in preparation for synaptic release. DAT is a principal regulator of cytoplasmic DA concentrations. Under normal physiological conditions, the DAT transports extracellular DA back into the nerve terminalPowerPoint Presentation: DAT is an integral membrane protein that removes dopamine from the synaptic cleft and deposits it into surrounding cells, thus terminating the signal of the neurotransmitter. DAT is a symporter that moves dopamine across the cell membrane by coupling the movement to the energetically-favorable movement of sodium ions moving from high to low concentration into the cellDopaminergic pathways in CNS: Dopaminergic pathways in CNS The nigrostraital pathway Accounts 75% of dopamine in brain. Consist cell bodies in substantia nigra with axons terminating in the corpus straitum. These fibres run in medial forebrain bundle along with other monoamine-containing fibres. The mesolimbic / mesocortical pathways Cell bodies occurs in group in midbrain and whose fibres projects, also via medial forebrain bundle, to parts of limbic system, especially the nucleus accumbens and the amygdaloids nucleus and to the frontal cortex.PowerPoint Presentation: The tuberohypophyseal system Is a group of short neurons running from ventral hypothalamus to the median eminence and pituitary gland, the secretions of which they regulate.DEGRADATION: DEGRADATIONPowerPoint Presentation: Functions cognition voluntary movement motivation and reward inhibition of prolactin production (involved in lactation) sleep, mood, attention, and learningPHARMACOLOGICAL ACTION: PHARMACOLOGICAL ACTION Cardiovascular Dopamine exerts a stimulatory effect on the β 1 receptors of the heart, having both inotropic and chronotropic effects. At very high doses, dopamine activates α receptors on the vasculature, resulting in vasoconstriction. Renal and visceral Dopamine dilates renal and splanchnic arterioles by activating dopaminergic receptors, thus increasing blood flow to the kidneys and other viscera.These receptors are not affected by α - or β -blocking drugs. Therefore, dopamine is clinically useful in the treatment of shock, in which significant increases in sympathetic activity might compromise renal functionPowerPoint Presentation: DEFICIENCY OF DOPAMINE Reduced ability to feel pleasure Flat, bored, apathetic and low enthusiasm Depressed Low drive and motivation Difficulty getting through a task even when interesting Difficulty paying attention and concentrating Slowed thinking and/or slow to learn new ideas Prone to addictions (e.g. alcohol) Low libido or impotence Mentally fatigued easily and physically fatigued easily Sleep too much and trouble getting out of bedRECEPTORS: RECEPTORS Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system Dopamine receptors are implicated in many neurological processes, including motivation, pleasure, cognition, memory, learning, and fine motor control, as well as modulation of neuro-endocrine signaling.CLASSIFICATION: CLASSIFICATION D₁-like family- D₁ and D₅ (excitatory nature) D₂-like family- D₂ D₃ and D₄ (inhibitory nature) RECEPTOR NAME TYPICAL LOCATIONS RESULT OF LIGAND BINDINGS D₁ , D₅ Brain, s m of the renal vascular bed Stimulation of adenyl cyclase & increased cAMP D₂ Brain, s m, presynaptic nerve terminals Inhibition of adenyl cyclase, increased potassium conductance D₃ Brain Inhibition of adenyl cyclase D₄ Brain, CVS Inhibition of adenyl cyclase D1 like family D2 like family: D1 like family D2 like familyLOCATION & FUNCTIONS OF DOPAMINE RECEPTORS IN CNS: LOCATION & FUNCTIONS OF DOPAMINE RECEPTORS IN CNS Functions Motor control Motor control Prolactin regulation Memory . Motivation and emotional response Memory . Motivation and emotional responsePowerPoint Presentation: DOPAMINE AGONISTS ANTAGONISTS Dopamine Chlorpromazine Apomorphine Haloperidol Bromocriptine Clozapine Sulpiride ↑ cAMP ↓ cAMPREFERENCE: ‘‘ Pharmacology’’ by Rang and Dale , 6 th edition , ELSEVIER Publications Lippincott’s ‘‘Pharmacology’’ by Richard D. Howland , Mary J. Mycek , 3 rd Lippincott williams & wilkins Publications. ‘‘Essentials of medical pharmacology’’ by KD Tripathi, 6 th edition, JAYPEE Publications. www.google.co.in REFERENCEPowerPoint Presentation: THANK you You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.