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1) Ç÷¾× ¹× ¸²ÇÁ°è : ¿ëÇ÷¼º ºóÇ÷, Àϰú¼º ¹éÇ÷±¸ °¨¼Ò, Ç÷¼ÒÆÇ °¨¼Ò µîÀÌ µå¹°°Ô º¸°íµÇ¾î ÀÖÀ¸¹Ç·Î ƯÈ÷ Àå±âÅõ¿©½Ã¿¡´Â Á¤±âÀûÀÎ Ç÷±¸¼ö ÃøÁ¤ ¹× °£¤ý½Å±â´É °Ë»ç¸¦ ½Ç½ÃÇÑ´Ù.
2) ´ë»ç ¹× ¿µ¾ç : ½Ä¿åºÎÁø
3) Á¤½Å°è : ¿ì¿ïÁõÀº ÆÄŲ½¼¾¾º´ ȯÀÚÀÇ ÀÓ»ó Áõ»óÀÇ ÀϺÎÀÏ ¼ö ÀÖÀ¸¸ç ÀÌ ¾àÀ» Åõ¿©ÇÑ È¯ÀÚ¿¡¼ ¹ß»ýÇÒ ¼ö ÀÖ´Ù. ÃÊÁ¶, ºÒ¾È, ºÒ¸é, ȯ°¢, ¸Á»ó, Àϰú¼º ¹æÇâ°¨°¢ »ó½ÇÀÌ Æ¯È÷ °í·ÉÀÚ³ª ÀÌ·¯ÇÑ º´·ÂÀÌ Àִ ȯÀÚ¿¡¼ ³ªÅ¸³¯ ¼ö ÀÖ´Ù. ½ÃÆÇ ÈÄ Á¶»ç¿¡¼ µµÆÄ¹Î Á¶Àý°ï¶õ ÁõÈıº(DDS : Dopamine dysregulation syndrome)ÀÌ º¸°íµÇ¾ú´Ù.
4) ½Å°æ°è : ¹Ì°¢ ¼Ò½Ç ¶Ç´Â ¹Ì°¢ÀÌ»óÀÌ ¸î ·Ê º¸°íµÇ¾ú´Ù. Ä¡·á Èı⿡ ¿îµ¿ ÀÌ»óÁõ(¹«µµº´ ¶Ç´Â ¹«Á¤À§ ¿îµ¿)ÀÌ ³ªÅ¸³¯ ¼ö ÀÖ´Ù. ÀÌ Áõ»óÀº ¿ë·® °¨¼Ò·Î »ç¶óÁö°Å³ª °¨¼ÒµÉ ¼ö ÀÖ´Ù. Ä¡·á Áö¼Ó ½Ã Ä¡·á ¹ÝÀÀ º¯µ¿ÀÌ ¹ß»ýÇÒ ¼ö ÀÖ´Ù. ÀÌ´Â µ¿ÀÛµ¿°á, ¾àÈ¿¼Ò½Ç, on-off Çö»óÀ» Æ÷ÇÔÇÑ´Ù. ÀÌ Áõ»óÀº ¿ë·® Á¶Àý ¹× ÀûÀº ¿ë·®À» ´õ ÀÚÁÖ Åõ¿©ÇÔÀ¸·Î½á Áõ»óÀÌ »ç¶óÁö°Å³ª °¨¼ÒµÉ ¼ö ÀÖ´Ù. ±× ÈÄ Ä¡·á È¿°ú¸¦ °È½Ã۱â À§ÇØ ¿ë·®À» ´Ù½Ã Áõ°¡½Ãų ¼ö ÀÖ´Ù. ÀÌ ¾àÀº Á¹À½°ú °ü·ÃÀÌ ÀÖÀ¸¸ç ¸Å¿ì µå¹°°Ô ³· ½Ã°£ µ¿¾ÈÀÇ Á¹À½ ¹× ±â¸é°ú °ü·ÃÀÌ ÀÖ¾ú´Ù.
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8) ÇǺΠ¹× ºÎ¼Ó±â°è : µå¹°°Ô ¼Ò¾çÁõ, ¹ßÁø °°Àº ¾Ë·¹¸£±â¼º ÇǺιÝÀÀÀÌ ³ªÅ¸³¯ ¼ö ÀÖ´Ù.
9) ±âŸ : ¶§¶§·Î À§Àå°üÃâÇ÷, È«Á¶, ¹ßÇÑ, Ç÷û ¿ä»ê, BUN »ó½Â, µå¹°°Ô °æ¹ÌÇÑ Æ®·£½º¾Æ¹Ì³ªÁ¦(ALT, AST), ALP »ó½ÂÀÌ ³ªÅ¸³¯ ¼ö ÀÖÀ¸¸ç gamma-Glutamyltransferase »ó½ÂÀÌ º¸°íµÇ¾ú´Ù. ¿ä°¡ ºÓ°Ô º¯»öµÉ ¼ö ÀÖ´Ù. ħ, Çô, Ä¡¾Æ ¶Ç´Â ±¸°Á¡¸·À» Æ÷ÇÔÇÑ ´Ù¸¥ ü¾× ¶Ç´Â Á¶Á÷ÀÌ º¯»ö(Èæ»ö µî)µÉ ¼ö ÀÖ´Ù.
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¼ö¼ú ÈÄ Ä¡·á Àç°³ ½Ã¿¡´Â ¼¼È÷ ¼ö¼ú Àü ¿ë·®±îÁö Áõ·®ÇÑ´Ù.
2) ÀÌ ¾à Åõ¿©¸¦ ÁßÁöÇÏÁö ¾ÊÀº »óÅ¿¡¼ ¼ö¼ú½Ã(ÀÀ±Þ½Ã µî)¿¡´Â ½ÃŬ·ÎÇÁ·ÎÆÇÀ̳ª ÇÒ·Îź¿¡ ÀÇÇÑ ¸¶Ãë´Â ÇÇÇÑ´Ù.
3) ÀÌ ¾à Åõ¿© Áß¿¡ ÀÌ»ó¹ÝÀÀÀÌ ³ªÅ¸³ªÁö ¾ÊÀ» °æ¿ì¿¡´Â Ä¡·áÈ¿°ú¸¦ Áõ°½Ã۱â À§ÇÏ¿© °è¼ÓÀûÀÎ ¿ë·® Áõ°¡¸¦ ½ÃµµÇØ º¼ ¼ö ÀÖ´Ù.
4) ÀÌ ¾àÀÇ Åõ¿©¸¦ °©ÀÚ±â ÁßÁöÇÏ´Â °æ¿ì¿¡´Â °í¿, ±Ù°Á÷, ½É¸®º¯È, Ç÷û Å©·¹¾ÆÆ¼´Ñ Æ÷½ºÆ÷Ű³ªÁ¦ Áõ°¡ µîÀ» ¼ö¹ÝÇÑ ½Å°æÀÌ¿ÏÁ¦¾Ç¼ºÁõÈıº(Neuroleptic Malignant Syndrome) À¯»çÁõ»óÀÌ ³ªÅ¸³¯ ¼ö ÀÖÀ¸¹Ç·Î Á¡Â÷ÀûÀ¸·Î °¨·®ÇÑ´Ù. À§ Áõ»óÀÌ º¹ÇÕÀûÀ¸·Î ³ªÅ¸³ª´Â °æ¿ì ÇÊ¿äÇϸé ÀÔ¿øÀ» Çϰí Áï½Ã ÀûÀýÇÑ ´ëÁõ¿ä¹ýÀ» ½Ç½ÃÇØ¾ß ÇÑ´Ù. ÀûÀýÇÑ Æò°¡ ÈÄ ÀÌ ¾àÀÇ Åõ¿©¸¦ Àç°³ÇÒ ¼ö ÀÖ´Ù.
5) ¿ì¿ïÁõÀº ÆÄŲ½¼¾¾º´ ȯÀÚÀÇ ÀÓ»ó Áõ»óÀÇ ÀϺÎÀÏ ¼ö ÀÖÀ¸¸ç ÀÌ ¾àÀ» Åõ¿©ÇÑ È¯ÀÚ¿¡¼ ¹ß»ýÇÒ ¼ö ÀÖ´Ù.
6) ÀÏ»ó»ýȰ¿¡¼ ±â¸éÁõÀÌ ¸Å¿ì µå¹°°Ô º¸°íµÇ¾ú´Ù. µû¶ó¼ ÀÌ ¾àÀÇ Åõ¿©½Ã ¿îÀüÀ̳ª ±â°èÁ¶ÀÛ¿¡ ÁÖÀǸ¦ ¿äÇÑ´Ù. Á¹À½ ¹×/¶Ç´Â ±â¸éÀ» °æÇèÇß´ø ȯÀÚ´Â ¿îÀüÀ̳ª ±â°èÁ¶ÀÛÀ» »ï°¡¾ß ÇÑ´Ù. ½ÉÇÒ °æ¿ì ¿ë·®°¨¼Ò³ª ÀÌ ¾àÀÇ Åõ¿© Áß´ÜÀ» °í·ÁÇÒ ¼ö ÀÖ´Ù.
7) ÀÌ ¾àÀ» Åõ¿© ¹ÞÀº ȯÀÚ¿¡¼ Ãæµ¿Á¶ÀýÀå¾Ö°¡ ³ªÅ¸³ª´ÂÁö ¸ð´ÏÅ͸µÇÏ¿©¾ß ÇÑ´Ù. ȯÀÚ ¹× º¸È£ÀÚ´Â ÀÌ ¾àÀ» ºñ·ÔÇÏ¿© ·¹º¸µµÆÄ¸¦ ÇÔÀ¯ÇÏ´Â µµÆÄ¹Î È¿´É¾àÀÇ Åõ¿©·Î ÀÎÇØ º´ÀûÀÎ µµ¹Ú, ¼º¿åÁõ°¡, ¼ºÇൿ°úÀ×, Ãæµ¿±¸¸Å, ´ë½ÄÁõ ¶Ç´Â °¹ÚÀû ½Ä»ç µîÀÇ Ãæµ¿Á¶ÀýÀå¾Ö°ú °ü·ÃµÈ ÇൿÁõ»óÀÌ ³ªÅ¸³¯ ¼ö ÀÖÀ½À» ¾Ë°í ÀÖ¾î¾ß ÇÑ´Ù. ÀÌ·¯ÇÑ Áõ»óÀÌ ³ªÅ¸³ª´Â °æ¿ì¿¡´Â Ä¡·áÀÇ Àç°ËÅä°¡ ±ÇÀåµÈ´Ù.
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Mechanism of Action
Levodopa¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ Striatal dopamine levels in symptomatic Parkinson's disease are decreased by 60 to 80%, striatal dopaminergic neurotransmission may be enhanced by exogenous supplementation of dopamine through administration of dopamine's precursor, levodopa. A small percentage of each levodopa dose crosses the blood-brain barrier and is decarboxylated to dopamine. This newly formed dopamine then is available to stimulate dopaminergic receptors, thus compensating for the depleted supply of endogenous dopamine.
Pharmacology
Levodopa¿¡ ´ëÇÑ Pharmacology Á¤º¸ Levodopa (L-dopa) is used to replace dopamine lost in Parkinson's disease because dopamine itself cannot cross the blood-brain barrier where its precursor can. However, L-DOPA is converted to dopamine in the periphery as well as in the CNS, so it is administered with a peripheral DDC (dopamine decarboxylase) inhibitor such as carbidopa, without which 90% is metabolised in the gut wall, and with a COMT inhibitor if possible; this prevents about a 5% loss. The form given therapeutically is therefore a prodrug which avoids decarboxylation in the stomach and periphery, can cross the blood-brain barrier, and once in the brain is converted to the neurotransmitter dopamine by the enzyme aromatic-L-amino-acid decarboxylase.
Metabolism
Levodopa¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Monoamine oxidase type A (MAO-A)Monoamine oxidase type B (MAO-B)Aromatic-L-amino-acid decarboxylase (AADC)
Protein Binding
Levodopa¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ High
Half-life
Levodopa¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 50 to 90 minutes
Absorption
Levodopa¿¡ ´ëÇÑ Absorption Á¤º¸ Levodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier system.
Pharmacokinetics
Benserazide HClÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
Benserazide hydrochloride :
Èí¼ö : °æ±¸ : ¾à 58%
´ë»ç : ÁÖ·Î ÀåÁ¡¸·¿¡¼, ÀϺΠ°£¿¡¼ ´ë»çµÊ
¼Ò½Ç : ´ëºÎºÐ ´ë»çü·Î¼ ½Å¼ÓÇÏ°Ô ½Å¹è¼³µÊ (12½Ã°£ À̳»¿¡ 85%)
Levodopa :
Èí¼ö : °í´Ü¹é ½ÄÀÌ¿Í °°ÀÌ Åõ¿©Çϸé ÀúÇ쵃 ¼ö ÀÖÀ½
¹Ý°¨±â : 1.2-2.3 ½Ã°£
¼Ò½Ç : Dopamine, norepinephrine, homovanillic acid·Î¼ ÁÖ·Î ½Å¹è¼³µÊ (80%)
Levodopa and Benserazide :
Èí¼ö : 66-74%°¡ ¼ÒÀå »óºÎ¿¡¼ Èí¼öµÊ
¹Ý°¨±â : levodopa : ¾à 45ºÐ
Ç÷ÁßÃÖ°í³óµµ µµ´Þ½Ã°£ :
MadoparⰒ : ¾à 1½Ã°£
MadoparⰒ HBS : ¾à 3½Ã°£
Biotransformation
Levodopa¿¡ ´ëÇÑ Biotransformation Á¤º¸ 95% of an administered oral dose of levodopa is pre-systemically decarboxylated to dopamine by the L-aromatic amino acid decarboxylase (AAAD) enzyme in the stomach, lumen of the intestine, kidney, and liver. Levodopa also may be methoxylated by the hepatic catechol-O-methyltransferase (COMT) enzyme system to 3-O-methyldopa (3-OMD), which cannot be converted to central dopamine.
Toxicity
Levodopa¿¡ ´ëÇÑ Toxicity Á¤º¸ Oral, mouse: LD50 = 2363 mg/kg; Oral, rabbit: LD50 = 609 mg/kg; Oral, rat: LD50 = 1780 mg/kg.
Drug Interactions
Levodopa¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
CYP450 Drug Interaction
[CYP450 TableÁ÷Á¢Á¶È¸]
Food Interaction
Levodopa¿¡ ´ëÇÑ Food Interaction Á¤º¸ Not Available
Drug Target
[Drug Target]
Description
Levodopa¿¡ ´ëÇÑ Description Á¤º¸ The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [PubChem]
Drug Category
Levodopa¿¡ ´ëÇÑ Drug_Category Á¤º¸ AntidyskineticsAntiparkinson AgentsDopamine Agents
Smiles String Canonical
Levodopa¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ NC(CC1=CC(O)=C(O)C=C1)C(O)=O
Smiles String Isomeric
Levodopa¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ N[C@@H](CC1=CC(O)=C(O)C=C1)C(O)=O
InChI Identifier
Levodopa¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1/f/h13H
Chemical IUPAC Name
Levodopa¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid
Drug-Induced Toxicity Related Proteins
LEVODOPA ÀÇ Drug-Induced Toxicity Related ProteinÁ¤º¸Replated Protein :Opioid growth factor receptor Drug :levodopa Toxicity :Parkinson's disease (PD). [¹Ù·Î°¡±â] Replated Protein :ParkinDrug :Levodopa Toxicity :dyskinesias. [¹Ù·Î°¡±â] Replated Protein :Catechol O-methyltransferase Drug :levodopa Toxicity :toxicity of levodopa. [¹Ù·Î°¡±â]
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