Neuroscience Online

Section I: Cellular and Molecular Neurobiology 12. Biogenic Amine Neurotransmitters Part 11 of 11 Jack C. Waymire, Ph.D.

Clinical Importance and Pharmacology

Dopamine - Clinical Importance and Pharmacology

Schizophrenia. The DA theory of schizophrenia is based on the observation that DA antagonists are effective antipsychotic drugs. Their capacity to inhibit DA receptors correlates well with their antipsychotic efficacy. Currently, clinical studies are attempting to develop DA antagonists with specific DA receptor subtype efficacy that will most effectively decrease the antipsychotic symptoms without influencing other DA actions, such as movement control. As mentioned in the anatomy section, an overactivity of the mesolimbic DA system appears especially prominent in schizophrenia.

Disorders of Movement Control. It is now well accepted that decreased DA in the substantia nigra and striatum is the critical lesion in Parkinson's disease. Autopsy shows that nearly all DA is lost during the course of this disease, apparently due to the degeneration of DA neurons. l-DOPA is used to treat this disease's symptoms because it can be converted to DA by AADC in the cells in the vicinity of the degenerated nerve endings to replace the missing endogenous DA. Some preparations of l-DOPA include a pherpheral AADC inhibitor so that more of the l-DOPA will be available for transport into the CNS. Conversion of l-DOPA into DA in the blood prevents its transport into the CNS. Other drugs that are effective in treating Parkinson's symptoms are DA agonists, as well as MAO and COMT inhibitors.

Cross Reference: Links for Dopamine

Norepinephrine - Clinical Importance and Pharmacology

Autonomic or Smooth Muscle Dysfunction. Drugs that interact with NE receptors are widely used to treat disorders involving autonomic or smooth muscle dysfunction such as asthma, coronary heart disease, angina pectoris, ventricular arrhythmias, migraine and hyperthyroidism. (See Table VI).

Cross Reference: Links for Norepinephrine

Serotonin - Clinical Importance and Pharmacology

Affective Disorders. Low levels of 5-HT and metabolites are associated with depression and especially a type of depression that is more likely to lead to suicide. Several studies have shown reduced 5-HT in brains of suicide victims as well as a low 5HIAA in CSF of depressed patients who have high incidence of suicide attempts. Recent studies indicate that this type of 5-HT influence may start early in life; low levels of 5HIAA have been found in children and adolescents with disruptive behavioral disorders. Some of the drugs that are effective antidepressant treatments are nonspecific with respect to their relative influence on NE versus 5-HT disposition, thus it has been difficult to know for certain which monoamine is responsible for the treatment effects. More recently selective serotonin reuptake inhibitors (termed SSRIs) have been introduced for the treatment of depression that are among the more effective drugs available for this purpose.

Obsessive Compulsive Disorder. 5-HT dysfunction has been associated with obsessive compulsive disorder. Accordingly, selective 5-HT uptake blockers are used as a therapy for this condition.

Aggression. Although controversial, 5-HT reuptake blockers are used for the treatment of aggression.

Eating Disorders. Also controversial is the use of the drug fenfluramine to treat eating disorders because of the toxic effects that occur in some individuals. Fenfluramine blocks 5-HT reuptake into nerve terminals.

Schizophrenia. A number of recently introduced antipsychotic drugs are producing favorable results in treating the symptoms of schizophrenia. These drugs are interesting pharmacologically in that they block both DA and 5-HT receptors as well as ACh and HA (Table VII, Olanzapine).

Migraine Headaches. 5-HT₁ agonists are used for the treatment of migraine headache.

Insomnia. The role of 5-HT in sleep regulation has lead to the hypothesis that reduced levels 5-HT may induce insomnia. Some clinicians are treating patients with 5-HT uptake blockers for this ailment.

Cross Reference: Links for Serotonin

Histamine - Clinical Importance and Pharmacology

Insomnia. The most popular treatment for insomnia is the use of over the counter CNS acting antihistamines.

Cross Reference: Links for Histamine

See the Table of Drugs that Interact with Monoamines.

Test Your Knowledge

13. Which of the following can be administered orally to increase dopamine levels in the CNS? (Note: There is more than one correct answer.)

A. Dopamine B. Tyrosine C. Acetyl coenzyme A D. l-DOPA E. l-DOPA plus an aromatic L-amino acid decarboxylase inhibitor