Sympathomimetic drug

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.

Mechanisms of action

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.

Direct-acting

Adrenergic receptor agonists

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

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

Indirect-acting

Norepinephrine transporter blockade

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.

Inhibition of epinephrine and norepinephrine metabolism

Inhibition of norepinephrine or epinephrine metabolism can produce sympathomimetic effects. Both are metabolized mainly by the enzyme monoamine oxidase (MAO), thus the monoamine oxidase inhibitor (MAOI) drugs can induce such effects. COMT inhibitors can also decrease metabolism of norepinephrine and epinephrine.

Structure Activity Relationship

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

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 therepeutic use and abuse potential, can induce tolerance, and possibly physical dependence.

Comparison

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

Examples

• 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)

See also

• Sympathetic nervous system

References

External links

• MeSH Amines,+Sympathomimetic
• Sympathomimetic+amine at eMedicine Dictionary
• Sympathomimetic at eMedicine Dictionary