Sympathomimetic drugs are stimulant compounds which mimic the effects of neurotransmitter 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 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.
- 1 Mechanisms of action
- 2 Structure-activity relationship
- 3 Structure-activity relationship
- 4 Cross-reactivity
- 5 Comparison
- 6 Examples
- 7 See also
- 8 References
- 9 External links
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 that increase the levels of endogenous catecholamines.
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.
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.
Norepinephrine and dopamine 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.
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. 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
Norepinephrine is synthesized by the body from the amino acid tyrosine, and is used in the synthesis of epinephrine, which is a stimulating neurotransmitter of the central nervous system. Thus, all sympathomimetic amines fall into the larger group of stimulants (see psychoactive drug chart). In addition to intended therapeutic use, many of these stimulants have abuse potential, can induce tolerance, and possibly physical dependence, although not by the same mechanism(s) as opioids or sedatives. The symptoms of physical withdrawal from stimulants can include fatigue, dysphoric mood, increased appetite, vivid or lucid dreams, hypersomnia or insomnia, increased movement or decreased movement, anxiety, and drug craving, as is apparent in the rebound withdrawal from certain substituted amphetamines. Physical withdrawal from some sedatives can be potentially lethal, for instance benzodiazepine withdrawal syndrome. Opioid withdrawal is very uncomfortable, often described as a bad case of the flu, with possibly severe abdominal cramps and diarrhoea as central symptoms, but it is rarely lethal unless the user has a comorbid condition.
- ephedrine (found in Ephedra)
- pseudoephedrine (also found in Ephedra species)
- maprotiline (Ludiomil)
- methylphenidate (Ritalin)
- lisdexamfetamine (Vyvanse)
- cocaine (found in Erythroxylum coca, coca)
- cathinone (found in Catha edulis, khat)
- cathine (also found in C. edulis)
- pemoline (Cylert)
- phenmetrazine (Preludin)
- propylhexedrine (Benzedrex)
- Medicinal Chemistry of Adrenergics and Cholinergics
- Campbell, Neil A.; Reece, Jane B. (2005). Biology (7th ed.). Pearson - Benjamin Cummings.
- Patestas, Maria A.; Gartner, Leslie P. (2006). A Textbook of Neuroanatomy. Blackwell Publishing.
- Longmore, Murray; Wilkinson, Ian B.; Davidson, Edward H.; Foulkes, Alexander; Mafi, Ahmad R. (2008). Oxford Handbook of Clinical Medicine (8th ed.). OUP Oxford.
- "Medscape Opioid Abuse, Treatment and Management".