 Dear students, in this module we shall discuss the neurotransmitters involved in slow and indirect transmission. There are two classes of such neurotransmitters. The first class includes the biogenic amines and the second class includes neuropeptides. First we shall discuss the biogenic amines. Biogenic amines act indirectly through second messenger pathways and produce slow synaptic responses. They include catecholamines that is epinephrine and norepinephrine and dopamine. They also include serotonin and histamine. We shall discuss the role of norepinephrine and epinephrine in detail. The neurons which release these hormones or neurotransmitters are called adrenergic neurons. Norepinephrine is the primary excitatory neurotransmitter in post-ganglionic cells of sympathetic nervous system. While epinephrine is excitatory at some synapses and inhibitory at others depending on the characteristics of post-synaptic membrane. Both these neurotransmitters are also released by the chromophine tissue of vertebrate adenal medulla. Both these neurotransmitters are structurally very similar having difference only on one methyl group. They also have similar pharmacological characteristics. Dear students, the norepinephrine is synthesized from amino acid phenylalanine. Dear students, when a neurotransmitter is released, it is necessary for it to stop its function. Norepinephrine is inactivated through two ways. In the first method, it is taken up by the cytoplasm of the presynaptic cell, i.e. the cell is reabsorbed by the neurotransmitter and the norepinephrine is repackaged and then released again when necessary. In the second method, when the presynaptic cell takes up the norepinephrine, an enzyme monoamide oxidase breaks it. In another method, the synaptic cleft is methylated by the norepinephrine and inactivates it. Dear students, there are certain psychoactive drugs which resemble in structure. These are the amines of the biogenic and also act at the same synapses at which these neurotransmitters bind. For example, mescaline, that is a drug that induces hallucinations. It interferes with the norepinephrine at synapses in the central nervous system. Another biogenic amine analogue is amphitamine. It is very potent central nervous system stimulant. It mimics norepinephrine and it interacts with the adrenergic neurotransmission. Another biogenic amine analogue is cocaine. It interferes with the inactivation of norepinephrine. When norepinephrine is not inactivated, it has a continuous effect on the neurotransmission. Now we shall discuss the neuropeptides, the second group involved in slow and indirect neurotransmission. There are about 40 or more neuropeptides involved in neurotransmission. They are synthesized and released in vertebrate central nervous system. Some neuropeptides are also produced outside the central nervous system by non-neural tissues. For example, intestinal endocrine cells also produce some neuropeptides, some autonomic neurons also produce some sensory neurons also produce some neuropeptides. Many of these neuropeptides are also found in the nervous system of invertebrates. Many hypothalamic and pituitary gland hormones are neuropeptides, similarly gastrointestinal hormones, glucagon, insulin, gastrin and cholecystokinin are also peptides. Neuropeptide and endorphins and encephalins are also examples. The neuropeptides are released in three ways as a neurotransmitter, as a neurosecretary substance and as a hormone. When a neuron secretes it and acts on other neurons, it is known as its role as a neurotransmitter. But when a neuropeptide is released in the circulatory system, it affects other neurons so such a substance is called neurosecretary, whereas endocrine tissues or endocrine glands as a substance are released and this substance affects non-neural tissues so that is called a peptide hormone. Neuropeptides are more potent neurotransmitters than small neurotransmitters. This is due to the reason that they bind in very low concentrations, they are active at 10 to the power 9 molar as compared to 10 to the power minus 5 molar of other substances. The second reason is that they act through second messenger pathways that provide amplification. So a small amount can produce large effect. The third reason of their effectiveness is that their actions are terminated very slowly so they remain available for long time to the receptors.