PHARMACOLOGY Chapter 28

Because dopamine has low bioavailability and does not readily cross the blood-brain barrier, its precursor, L-dopa (levodopa), is used. This amino acid enters the brain via an L-amino acid transporter (LAT) and is converted to dopamine by the enzyme aromatic L-amino acid decarboxylase (dopa decarboxylase),

An ergot alkaloid. bromocriptine acts as a partial agonist at dopamine D2 receptors in the brain. The drug increases the functional activity of dopamine neurotransmitter pathways, including those involved in extrapyramidal functions

This non-ergot has high affinity for the dopamine D3 receptor

Another non-ergot, this drug has high affinity for the dopamine D2 receptor. It is effective as monotherapy and can be used with levodopa to smooth out response fluctuations

A potent dopamine receptor agonist, apomorphine injected subcutaneously may provide rapid (within 10 min) but temporary relief (1–2 h) of "off-periods" of akinesia in patients on optimized dopaminergic therapy

Selegine and rasagilene are selective inhibitors of monoamine oxidase type B, the form of the enzyme that metabolizes dopamine

Entacapone and tolcapone are inhibitors of COMT, the enzyme in both the CNS and peripheral tissues (Figure 28–2) that converts levodopa to 3-O-methyldopa (3OMD).

Amantadine enhances dopaminergic neurotransmission by unknown mechanisms that may involve increasing synthesis or release of dopamine or inhibition of dopamine reuptake. The drug also has muscarinic blocking actions

The drugs (eg, benztropine, biperiden, orphenadrine) decrease the excitatory actions of cholinergic neurons on cells in the striatum by blocking muscarinic receptors.

Physiologic and essential tremor are clinically similar conditions characterized by postural tremor. The conditions may be accentuated by anxiety, fatigue, and certain drugs, including bronchodilators, tricyclic antidepressants, and lithium. They may be alleviated by -blocking drugs including propranolol

Drug therapy usually involves the use of amine-depleting drugs (eg, reserpine, tetrabenazine ), the latter having less troublesome adverse effects. Dopamine receptor antagonists (eg, haloperidol, perphenazine ) are also sometimes effective.

Tourette's syndrome is a disorder of unknown cause that frequently responds to haloperidol and other dopamine D2 receptor blockers, including pimozide

Parkinsonism symptoms caused by antipsychotic agents (see Chapter 29) are usually reversible
In acute dystonias, parenteral administration of benztropine or diphenhydramine is helpful

Treatment involves use of the chelating agent penicillamine (dimethylcysteine), which removes excess copper.

Dopaminergic therapy is the preferred treatment, and ropinirole , a long-acting drug, is approved for this condition. Opioid analgesics and benzodiazepines are also used.