In addition to successful dopaminergic-based therapies, antimuscarinic anticholiner-
gic agents (see section 4.2.5) are also used as antiparkinsonism drugs, because the
removal of inhibiting dopaminergic effects exaggerates the excitatory cholinergic func-
tions in the striatum. Antagonists at muscarinic cholinoceptors, such as benztropine
(4.80) or biperiden (4.108), suppress striatal cholinergic overactivity in the brain,
thereby improving tremor and to a lesser extent rigidity; akinesia, however, is not
helped by such agents. (On the other hand, the dopaminergic agents work well for aki-
nesia, but do poorly against the tremor symptoms.)
There are many complications in the manipulation of dopamine and acetylcholine
receptors for the treatment of Parkinson’s disease. As discussed, anticholinergics are of
benefit for the tremor of Parkinson’s. However, a dementia can sometimes accompany
Parkinson’s disease and, as discussed in section 4.2.6, anticholinergics may in fact
worsen symptoms of dementia. Also, there is an inverse relationship between Parkinson’s
disease and psychosis. Parkinson’s disease is a deficiency of dopamine and is treated
with dopaminergics; psychosis is symptomatic of an excess of dopamine and is treated
with antidopaminergics. A side effect of treating Parkinson’s disease with dopaminer-
gics is confusion and psychotic delusions; a side effect of treating psychosis with
antidopaminergics is the development of parkinsonian features (e.g., resting tremor,
stumbling gait).
4.5 SEROTONIN AND THE SEROTONERGIC RECEPTORS
Serotonin (4.109, 5-hydroxytryptamine, 5-HT) is a central neurotransmitter that is also
found peripherally in the intestinal mucosa and in blood platelets, where its role is incom-
pletely elucidated; it even occurs in plants such as bananas. Although there is an enormous
literature on the biochemistry and pharmacology of serotonin, our knowledge of its
biological role remains somewhat fragmented. The diverse physiological effects of
5-HT influence the cardiovascular system, the cerebrovascular system, the digestive
NEUROTRANSMITTERS AND THEIR RECEPTORS 249