The adrenergic drugs

The adrenergic drugs affect receptors that are stimulated by norepinephrine (noradrenaline) or epinephrine (adrenaline). These receptors are known as adrenergic receptors or adrenoceptors. Adrenergic drugs that activate adrenergic receptors are termed sympathomimetic, and drugs that block the activation of adrenergic receptors are termed sympatholytics.
Adrenergic neurons release norepinephrine as the primary neurotransmitter. These neurons are found in the central nervous system (CNS) and also in the sympathetic nervous system.
Neurotransmission involves the following steps:
1. Synthesis of norepinephrine:
Tyrosine is transported by a carrier into the adrenergic neuron, where it is hydroxylated to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase. This is the rate-limiting step in the formation of norepinephrine. DOPA is then decarboxylated by the enzyme aromatic I-amino acid decarboxylase to form dopamine in the presynaptic neuron.
2-storage: Dopamine enters a vesicle and is converted to norepinephrine. Norepinephrine is protected from degradation in the vesicle. Transport into the vesicle is inhibited by Reserpine.
3-Release of Neurotransmitter: Influx of calcium causes fusion of the vesicle with the cell membrane in a process known as exocytosis. Release is blocked by Guanethidine.
4-Binding to receptors: Norepinephrine released from the synaptic vesicles diffuses into the synaptic space and binds to postsynaptic receptors on the effector organ or to presynaptic receptors on the nerve.
5-Removal of norepinephrine:
1) Diffuse out of the synaptic space and enter the systemic circulation;
2) Be metabolized to inactive metabolites by catechol-O-methyltransferase (COMT) in the synaptic space; or
3) Undergo reuptake back into the neuron. that can be inhibited by tricyclic antidepressants (TCAs), such as imipramine, by serotonin–norepinephrine reuptake inhibitors such as duloxetine, or by cocaine . Reuptake of norepinephrine into the presynaptic neuron is the primary mechanism for termination of its effects.