擬腎上腺性藥物

主條目:藥物影響腎能素

吳宗穎藥師整理，有錯請多指教~

藥名	環 *catechol(兒茶酚胺): 是COMT的substrate，所以會被代謝(口服的BA差。如果不是兒茶酚胺則可以提升口服BA) **C4’-OH為beta-agonist所必須 **alpha-agonist則用C3’-OH *phenyl則是有direct and indirect效用 *並且減少苯環上的-OH可以增加脂溶性而增加CNS中的濃度。	C1(beta-C(依amine命名)) *direct effect:(R) Direct-acting agonist often has beta-OH, although dopamine is not.	C2(alpha-C(依amine命名)) *direct:(S) *indirect:(R) Substitution on alpha-C block the oxidation of MAO and increase t1/2 Enhances their ability to displace catecholamines from storage sites in noradrenergic nerve. Ex. Alpha-methyl comp’d are called phenylisopropylamine	N-R *αagonist: epi>NE>isoproterenol *βagonist: NE<epi<isoproterenol *如果N-alkyl比isopropyl大則對αreceptor的affinity會增加，但是intrinsic activity沒有
Norepinephrine(noradrenaline)(levarterenol)	catechol(兒茶酚胺)	C1-OH	X	X
epinephrine(adrenaline)	catechol(兒茶酚胺)	C1-OH	X	methyl
Isoproterenol (isoprenaline) nonselective beta-agonist	catechol(兒茶酚胺)	C1-OH	X	isopropyl
1.      改環為非catechol 2.      C2-substituents 3.      N-substituent 其中的1使drug不成為COMT的substrate 2和3使drug不成為MAO的substrate 只有其中一種延長duration的效果不明顯，但是如果同時兩種都有則會有明顯效果
alpha1-selectivity: phenylethylamine
Midodrine(a prodrug) Drug for autonomic failure-caused orthostatic hypotention →desglymidodrine, a α1-agonist
Phenylephrine Nasal decongestant	C3’-OH	C1-OH	X	Me
alpha1-selectivity: phenylpropylamine之phenylpropanolamine(indirect action)
Metaraminol Meta-hydroxy	C3’-OH	C1-OH	Me	X Direct&indirect acting(所以mixed action(對各種adrenergic受體皆有作用))
Methoxamine 2,5-dimethoxy	非典型	C1-OH	Me	X
alpha1-selectivity: imidazole der.:2-arylimidazoline(=phenyl+methylene+imidazoline) 有phenylethylamine的general skeleton ~zoline、~metazolin(strang! no meta-substituents) 於生理pH值下會protonated，所以used externally as nasal decongestant or eye drops.
Naphazoline Naphthacene 較短效(易反彈)	meta-,para- lipophilic substituents	methylene	Imidazoline
Tetrahydrozoline 較短效(易反彈)	meta-,para- lipophilic substituents	methylene	Imidazoline
Xylometazoline 較長效(不易反彈)	meta-,para- lipophilic substituents	methylene	Imidazoline
Oxymetazoline Meta-hodroxy,比xylometazoline多m-hydroxy 較長效(不易反彈)	meta-,para- lipophilic substituents	methylene	Imidazoline
alpha2-selectivity:imidazole der.:2-arylimidazoline
Dexmedetomidine Its primary indication(適應症) is for sedation of initially intubated(插管?) and mechanically ventilated(上呼吸器) patients during treatment in an intensive care setting(加護病房)
alpha2-selectivity: imidazole der.:2-aminoimidazoline methylene of 2-arylimidazoline改成amino
clonidine α2A agonist antihypertensives 作用在中樞，所以算是一種CNS-depressant	ortho- lipophilic substituents	amino	Imidazoline
aparaclonidine α2A agonist =para-amino clonidine treat glaucoma(topical)	ortho- lipophilic substituents	amino	Imidazoline
bromonidine α2A agonist first-line agent for glaucoma CNS side effect M by aldehyde oxidase	ortho- lipophilic substituents	amino	Imidazoline
tizanidine α2C agonist presynaptic inhibition of motor neurons atα2C-adrenergic receptor site, thus it act as centrally acting muscle relaxant to treat chronic spasm	ortho- lipophilic substituents	amino	Imidazoline
alpha2-selectivity: guanidine: ring-opened analogue of clonidines at least one ortho-chlorine or methyl gr. On phenyl ring 2 antihypertensives
Guanabenz	ortho- lipophilic substituents (Cl)	imine+ guanidine
Guanafacine	ortho- lipophilic substituents (Cl)	keto+ guanidine
alpha2-selectivity: phenylpropylamine structurally unrelated to aminoimidazoline and guanidines
methyldopa(Aldomet) Methyldopate ethyl ester hydrochloride ↓ L-α-methyldopa(Aldomet) (prodrug): can pass BBB ↓aromatic L-amino ↓acid decarboxylase ↓(dopa decarboxylase) α-methyldopamine ↓ 1R,2S-α-methylnorepinephrine (active) antihypertensive drug	catechol	1R-OH	2S-Me	X
beta2-agonist: phenylethanolamine: noncatechol
Metaproteranol (Orciprenaline) short-acting	Resorcinol der. 仍activate beta1 receptor
terbutaline short-acting Bronchodilator and Halting the contraction of premature labor	Resorcinol der.
albuterol =salbutamol (racemate) short-acting bronchodilation	3’-hydroxymethyl and 4’-hydroxy (increase beta2 selectivity)	1R-OH	X	N-tBu
levalbuterol (Xopenex) (R)-enantiomer short-acting	3’-hydroxymethyl and 4’-hydroxy (increase beta2 selectivity	1R-OH	X	N-tBu
Pirbuterol short-acting inhalation	2’-hydroxymethyl and 3’-hydroxy (increase beta2 selectivity pyridine	1R-OH	X	N-tBu
salmeterol (Serevent) long-acting slow-onset	3’-hydroxymethyl and 4’-hydroxy (increase beta2 selectivity	1R-OH	X	big N-alkyl
formeterol (Foradil) long-acting fast-onset (R,R)-(-)-isomer is more potent	3’-formylamino and 4’-hydroxy	1R-OH	X	big N-alkyl alkoxyphenylalkyl
ritodrine short-acting relaxing uterine muscle and inhibit the constriction of premature labor	4’-OH	1R-OH	2-Me	big N-alkyl hydroxyphenylalkyl
Bitolterol(prodrug) short-acting	catechol being transferred to 4-methylbenzoic acid esters(D-toloyl) inhalant	1R-OH	X	N-tBu
beta2-agonist: phenylethanolamine: catechol
colterol (parent drug)	catechol duration shorter than bitolterol for susceptible to COMT	1R-OH	X	N-tBu
beta1-agonist: phenylethylamine: catechol 常用dopaminergic agent代替. 因為只活化beta1而較無beta2,所以比較不會引起tachycardia
Dopamine Dopaminergic agonist and direct/indirect beta1-agonist	catechol	X	X	X
Dobutamine Isobutyl Foye: Racemic, S-(-)-enantiomer is active Katzung 12th: Indeed, its action is not mediated by beta1 selectivity, S-(-)-enantiomer: α1-agonist R-(+)-enantiomer: α1-antagonist, β1-agonist	catechol	X	X	hydroxyphenylalkyl
prenalterol
Beta3-agonist: phenylethylamine:
mirabegron (美國商品名Myrbetriq，AstellasPharma藥廠)(歐洲商品名Betmiga貝坦利)
mixed-acting agonist: phenylethylamine indirect acting
tyramine(酪胺)
mixed-acting agonist: phenylethanolamine direct acting
NE	catechol	1R-OH	X	X
epi	catechol	1R-OH	X	N-Me
mixed-acting agonist: (+)-phenylpropanolamine=PPA=norephedrine
D-(-)-ephedrine(麻黃素)	benzene		1-hydroxy,2-methyl(1R:2S)或是(1S:2R) mixtures of erythro diastereomer	N-methyl
L-(+)-pseudoephedrine (偽麻黃素) 可以合成methamphetamine	benzene		1-hydroxy,2-methyl(1R:2R)或是(1S:2S) mixtures of threo diastereomer Fewer CNS side effect No direct agonist activity 常見解鼻充血藥	N-methyl
norephedrine =PPA 麻黃鹼的還原性產物(心血管毒性)	benzene		1-hydroxy,2-methyl(1R:2S)或是(1S:2R) mixtures of erythro diastereomer mostly indirect activity	沒有取代基
pseudonorephedrine	benzene		1-hydroxy,2-methyl(1R:2R)或是(1S:2S) mixtures of threo diastereomer	沒有取代基
metaraminol
mixed-acting agonist: phenylisopropylamine
S-(+)-amphetamine	benzene		alpha-methyl	沒有取代基
S-(+)-methamphetamine(N-methylamphetamine)	benzene		alpha-methyl	N-methyl

延伸學習

• 苯乙胺類似物

藥品學名	親脂基團	中間	胺	其他
isoproterenol	兒茶酚胺類	bata-hydroxy	N-isopropyl
epinephrine	兒茶酚胺類	bata-hydroxy	N-methyl
norepinephrine	兒茶酚胺類	beta-hydroxy	沒有取代基
ephedrine	benzene	1-hydroxy,2-methyl(1R:2S)或是(1S:2R)	N-methyl
pseudoephedrine	benzene	1-hydroxy,2-methyl(1R:2R)或是(1S:2S)	N-methyl
norephedrine	benzene	1-hydroxy,2-methyl(1R:2S)或是(1S:2R)	沒有取代基
pseudonorephedrine	benzene	1-hydroxy,2-methyl(1R:2R)或是(1S:2S)	沒有取代基
amphetamine	benzene	alpha-methyl	沒有取代基
methamphetamine	benzene	alpha-methyl	N-methyl
methamphetamine's enantiomer crank 有高度成癮性的甲基安非他命對掌異構物	benzene	alpha-methyl	N-methyl