Indirectly acting sympathomimetics

Indirectly acting sympathomimetics release noradrenaline from noradrenergic stores. The indirect sympathomimetics are derivatives of phenylethylamine. Due to their high lipophilicity, they can pass the blood-brain barrier relatively easily.

The two most important representatives are amphetamine and methyl penidate. Furthermore also modafinil, ephedrine, tyramine and norephedrine (see figure).

The effects of indirect sympathomimetic drugs are exclusively based on the stimulation of α and

β1 adrenoreceptors back:

Peripheral effects: blood pressure increase, often in combination with reflex bradycardia

CNS-effects: depending on the lipophilicity of the substances (amphetamines are strongly lipophilic and therefore also strongly effective on the central nervous system - excitatory, psychostimulant - e.g. methylphenidate; ephedrine and norephedrine have only a weakened central nervous system effect with moderate lipophilicity) The CNS effects are caused by the transporter-mediated release of serotonin, dopamine and norepinephrine. A relatively rapid development of a tolerance (tachyphylaxis) is characteristic, which is due to a depletion of the memory by repeated application.

Indirect sympathomimetic effect: Some direct-acting sympathomimetic drugs also have an indirect sympathomimetic effect, such as dopamine.

Addictive potential: Amphetamines have a high addictive potential. They are therefore subject to the narcotics prescription ordinance (BtMVV). The psychostimulant effects are particularly pronounced with methylenedioxyamphetamine (MDMA, designer drug Ecstasy).

Indirectly acting sympathomimetics are also found in natural substances, such as tyramine (cheese), norephedrine (leaves of the catatrine shrub), ephedrine (in the herb of Ephedra sinica.) Tyramine, ephedrine and norephedrine are of no great importance as pharmaceuticals. Ephedrine is offered together with other drugs as an influenza drug, norephedrine as an appetite suppressant.

1. Graefe KH (2016) Sympathetic nervous system. In: Graefe KH et al (Ed.) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S. 85-103
2. Rasmussen N et al (2016) History full circle: 'Novel' sympathomimetics in supplements. Drug Test Anal 8(3-4):283-286.