Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart rate, force of cardiac contraction, and blood pressure.
These drugs can act through several mechanisms, such as directly activating postsynaptic receptors, blocking breakdown and reuptake of certain neurotransmitters, or stimulating production and release of catecholamines.
Mechanisms of action
The mechanisms of sympathomimetic drugs can be direct-acting (direct interaction between drug and receptor), such as α-adrenergic agonists, β-adrenergic agonists, and dopaminergic agonists; or indirect-acting (interaction not between drug and receptor), such as
,
, release stimulants, and reuptake inhibitors that increase the levels of endogenous catecholamines.
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.
The presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha- and beta-adrenergic activity.
For maximum sympathomimetic activity, a drug must have:
-
Amine group two carbons away from an aromatic group
-
A hydroxyl group at the chiral beta position in the R-configuration
-
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 if the substituent is not bulky, then it will favor the alpha adrenergic receptors.
Direct-acting
Adrenergic receptor agonists
Direct stimulation of the α- and β-adrenergic receptors can produce sympathomimetic effects.
Salbutamol is a widely used direct-acting β
2-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
Dopaminergic stimulants such as
amphetamine,
ephedrine, and
propylhexedrine work by causing the release of dopamine and norepinephrine, along with (in some cases) blocking the reuptake of these neurotransmitters.
Abuse potential
Illegal drugs such as
cocaine and
MDMA also affect
dopamine,
serotonin, and
norepinephrine.
Norepinephrine is synthesized by the body from the amino acid tyrosine,
Sympathomimetic drugs are sometimes involved in development of cerebral vasculitis and generalized polyarteritis nodosa like diseases involving immune-complex deposition. Known reports of such hypersensitivity reactions include the use of pseudoephedrine,
Comparison
"Parasympatholytic" and "sympathomimetic" have similar effects, but through completely different pathways. For example, both cause
mydriasis, but parasympatholytics reduce accommodation (
cycloplegia) while sympathomimetics do not.
Examples
See also
External links
