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a compound derived from ammonia by replacing hydrogen atoms by univalent hydrocarbon radicals (同)aminoalkane

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/25 20:16:13」(JST)

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Epinephrine

Norepinephrine

Dopamine

Chemical structures of catecholamines.

Sympathomimetic drugs mimic the effects of transmitter substances of the sympathetic nervous system such as catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine, etc. Such drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.

These drugs act at the postganglionic sympathetic terminal,^[1] either directly activating postsynaptic receptors, blocking breakdown and reuptake, or stimulating production and release of catecholamines.

1 Mechanisms of action
2 Structure-activity relationship
- 2.1 Direct-acting
  - 2.1.1 Adrenergic receptor agonists
  - 2.1.2 Dopaminergic agonists
- 2.2 Indirect-acting
  - 2.2.1 Norepinephrine and Dopamine transporter blockade
3 Structure-activity relationship
4 Cross-reactivity
5 Comparison
6 Examples
7 See also
8 References
9 External links

Mechanisms of action[edit]

The mechanisms of sympathomimetic drugs can be direct-acting, such as α-adrenergic agonists, β-adrenergic agonists, and dopaminergic agonists; or indirect-acting, such as MAOIs, COMT inhibitors, release stimulants, and reuptake inhibitors that increase the levels of endogenous catecholamines.

Structure-activity relationship[edit]

For maximum sympathomimetic activity a drug must have the following; 1. Amine group two carbons away from an aromatic group. 2. A hydroxyl group at the chiral beta position in the R-configuration 3. Hydroxyl groups in the meta and para position of the aromatic ring to form a Catechol which is essential for receptor binding

The structure can be modified to alter binding. If the amine is primary or secondary it will have direct action, but if the amine is tertiary it will have poor direct action. Also if the amine has bulky substituents then it will have greater Beta adrenergic receptor activity, but it the substituent is non-bulky then it will favor the alpha adrenergic receptors.

Direct-acting[edit]

Adrenergic receptor agonists[edit]

Main article: Adrenergic agonist

Direct stimulation of the α- and β-adrenergic receptors can produce sympathomimetic effects. Salbutamol is a very commonly used direct-acting β₂-agonist. Other examples include phenylephrine, isoproterenol, and dobutamine.

Dopaminergic agonists[edit]

Stimulation of the D1 receptor by dopaminergic agonists such as fenoldopam is used intravenously to treat hypertensive crisis.

Indirect-acting[edit]

Norepinephrine and Dopamine transporter blockade[edit]

Classical sympathomimetic drugs are amphetamines (including MDMA), ephedrine, and cocaine, which act by blocking and reversing norepinephrine transporter (NET) activity. NET is a transport protein expressed on the surface of some cells that clears noradrenaline and adrenaline from the extracellular space and into cells, terminating the signaling effects.

Structure-activity relationship[edit]

A primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity. The pKa of the amine is approximately 8.5-10.^[2] 1- Substitution on aromatic ring-

The presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha and beta activity

Cross-reactivity[edit]

Substances like cocaine also affect dopamine, and some substances like MDMA affect serotonin.

Norepinephrine is synthesized by the body into epinephrine, causing central nervous system stimulation. Thus, all sympathomimetic amines fall into the larger group of stimulants (see psychoactive drug chart). Many of these stimulants have therapeutic use and abuse potential, can induce tolerance, and possibly physical dependence. Stimulates do not produce physical dependence in a way like opioids or sedatives will. The symptoms of physical withdrawal from stimulates are commonly described as being tired, sluggish, or general non-motivation. Physical withdrawal from most Sedatives can be potentially lethal. Opioid withdrawal is very uncomfortable, often describes as a bad case of the flu, but not lethal unless the user has an underlying condition.

Comparison[edit]

"Parasympatholytic" and "sympathomimetic" are similar, but not identical. For example, both cause mydriasis, but parasympatholytics reduce accommodation (cycloplegia) while sympathomimetics do not.

Examples[edit]

ephedrine (found in Ephedra)
pseudoephedrine (also found in Ephedra species)
amphetamine
methamphetamine
methylphenidate (Ritalin)
lisdexamfetamine (Vyvanse)
cocaine (found in Erythroxylum coca, Coca)
cathinone (found in Catha edulis, Khat)
cathine (also found in Catha edulis)
methcathinone
benzylpiperazine (BZP)
methylenedioxypyrovalerone (MDPV)
4-methylaminorex
pemoline (Cylert)
phenmetrazine (Preludin)
propylhexedrine (Benzedrex)

References[edit]

^ "Dorlands Medical Dictionary:sympathomimetic".
^ Medicinal Chemistry of Adrenergics and Cholinergics

External links[edit]

Amines, Sympathomimetic at the US National Library of Medicine Medical Subject Headings (MeSH)
Sympathomimetic+amine at eMedicine Dictionary
Sympathomimetic at eMedicine Dictionary

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Japanese Journal

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三上栄一,大野勉,岡尚男,石原廣男
医療薬学 = Japanese journal of pharmaceutical health care and sciences 31(1), 52-57, 2005-01-10
… FEN derivative), which has caused life-threatening liver damage and mazindol (MAZ), a sympathomimetic amine similar to an amphetamine. …
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