 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 are 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 chromophilic tissue of vertebrate adenyl 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. 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 which has been released can be reabsorbed and repackaged by the norepinephrine. The second method is the presynaptic cell which is taken up by the norepinephrine. After this, 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 to the biogenic amines and also act at the same synapses at which these neurotransmitters bind. We call these anti-drugs analogs. For example, mescaline, a biogenic amine analog, that is a drug that induces hallucinations. It interferes with the norepinephrine at synapses in the central nervous system. Another biogenic amine analog is amphetamine. It is a very potent central nervous system stimulant. It mimics norepinephrine and it interacts with the adrenergic neurotransmission. Another biogenic amine analog 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 and ocarine cells also produce some neuropeptides. Some autonomic neurons are also produced and some sensory neurons also produce neuropeptides. Many of these neuropeptides are also found in the nervous system of invertebrates. We will take some examples of neuropeptides. Many hypothalamic and pituitary gland hormones are neuropeptides. Similarly, gastrointestinal hormones, glucagon, insulin, gastrin, and cholecystokinin are also peptides. Similarly, substance PE 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, this is known as its role as neurotransmitter. But when a neuropeptide is released in a circulatory system but affects other neurons, then such a substance is called neurosecretary. Whereas endocrine glands or endocrine tissues release such substances. And when this substance affects non-neural tissues, 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 H2 power 9 molar as compared to 10 H2 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.