| Sažetak (engleski) | Appreciation of the role of dopamine in the brain, as a transmitter
and as a precursor of noradrenaline, came in mid-1960s when a combination of neurochemistry
and neuropharmacology led to many important discoveries about the
role of central nervous system transmitters, and about ability of drugs to influence
these systems.
There are three main dopaminergic pathways in the CNS: nigrostriatal, mesolimbic
and tuberoinfundibular.
There are two main families of dopamine receptor, D1 and D2, linked, respectively, to
stimulation or inhibition of adenylate cyclase. There are further divided into subtypes.
Most of the known functions of dopamine appear to be mediated by receptors of
D2 family.
Two main diseases are conected with dopamine and dopaminergic receptors: shizophrenia
and Parkinson's disease. Shizophrenia is a psychotic illness characterised
by delusions, hallucinations and thought disorder, together with social withdrawal
and often dementia. Pharmacological evidence is generally consistent with dopamine
overactivity hypothesis, but there is some evidence for involvement of serotoninrgic
system. Neuroleptics, also known as antipsychotic agents, are used in the symptomatic
management of psychoses, including shizophrenia and mania. They are believed
to owe their action to competitive antagonist properties at dopaminergic receptors in
the brain. Some neuroleptics are also been imployed in anesthetic procedures and in
certain neuropsychiatric disorders. There are few main chemical categories of neuroleptic
drugs: the so called, typical neuroleptics include the phenotiazines, the butyro-
phenones, and the thioxantenes while »atypical« neuroleptics include the benzamides
and the dibenzodiazepines.
Parkinson's disease is associated with a deficiency of nigrostriatal dopaminergic neurons.
lt is a progressive disorder of movement that occurs most commonly in the elderly,
and the main symptoms are tremor, muscle rigidity and decreases in the frequency
of voluntary movements. Drugs used in parkinsonism act by counteracting
deficiency of dopamine in basa! ganglia, like L-dopa, bromocriptin, selegilin, or by
blocking muscarinic receptors, like biperiden. Newer drugs act by blocking N-metyl-
D-aspartat (NMDA) receptors for aminoacids glutamat and aspartat.
Both, antiparkinsonic drugs as well as neuroleptics cause many side effects that
must be treated properly. For example, L-dopa may cause aritmia, nausea, vomiting,
hypotension and neuropleptics often cause, the so-c.alled extrapiramidal symptoms
which include parkinsonism, akatisia, tardive diskinesia. That is the reason why the
investigation of new drugs with specific act and minimal side-effects is in permanent
progress. |
