Dopamine amantadine

Dopaminergic drug are drug that affect the dopamine content of the brain. These drag include levodopa (Larodopa), carbidopa(Ladosyn), amantadine (Symmetrel),... 

Because chronic cocaine use appears to reduce the efficiency of central dopamine neurotransmission, a number of dopaminergic compounds, including amantadine, bromocriptine, mazindol, and methylphenidate, have been examined as treatments for cocaine abuse. It is thought that these relatively slow-onset dopaminergic agents, with low or relatively low abuse potential, would correct the dopamine dysregulation and alleviate withdrawal symptoms following chronic stimulant use. 

Opioids, benzodiazepines, barbiturates, corticosteroids, dopamine agonists (e.g., amantadine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole), H2-receptor antagonists, anticholinergics (e.g., diphenhydramine, trihexylphenidyl), P-adrenergic blockers, clonidine, methyldopa, carbamazepine, phenytoin, baclofen, cyclobenzaprine, lithium, antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), and interleukin-2... 

Add other PD medications (dopamine agonist, selegiline, amantadine, or COMT inhibitor)... 

Dopamine-Stimulating Medications. A variety of drugs that increase the availability of dopamine have been studied in cocaine addicts including L-DOPA, bupropion, amantadine, and methylphenidate. In small uncontrolled trials, these have shown some benefit, but definitive studies have yet to be performed. In addition, some dopamine-stimulating medications (in particular, the stimulants like methylphenidate or the amphetamines) are themselves subject to abuse, though, of note, this is typically not a problem when they are prescribed to patients who do not have a history of substance abuse such as, for example, in the treatment of attention deficit-hyperactivity disorder. 

In medical practice, four types of dopaminergic drags are used, and they can be characterized as dopamine precursors (levodopa), dopamine-releasing drugs (amantadine), dopamine receptor agonists (bromocriptine), and dopamine inactivation inhibitors (selegiline). 

Pharmacology The exact mechanism of action is unknown, but amantadine is thought to release dopamine from intact dopaminergic terminals that remain in the substantia nigra of parkinson patients. 

Amantadine is an old drug with several pharmacological properties warranting its (empirical) use in Parkinson s disease facilitation of dopamine release, blockade of dopamine re-uptake, anticholinergic effect, blockade of NMDA receptors. Amantadine is usually employed early in the disease process (monotherapy, 100 mg b.i.d.) and most often in combination with levodopa in more advanced stage disease (anti-dyskinesia effect ). 

Amantadine was originally introduced as an antiviral compound (see Chapter 50), but it is modestly effective in treating symptoms of parkinsonism. It is useful in the early stages of parkinsonism or as an adjunct to levodopa therapy. Its mechanism of action in parkinsonism is not clear, but amantadine may affect dopamine release and reuptake. Additional sites of action may include antagonism at muscarinic and A-methyl-D-aspartate (NMDA) receptors. Adverse effects include nausea, dizziness, insomnia, confusion, hallucinations, ankle edema, and livedo reticularis. Amantadine and the anticholinergics may exert additive effects on mental functioning. 

Mechanism of Action A dopaminergic agonist that blocks the uncoating of influenza A virus, preventing penetration into the host and inhibiting M2 protein in the assembly of progeny virions. Amantadine also blocks the reuptake of dopamine into presyn-aptic neurons and causes direct stimulation of postsynaptic receptors. Therapeutic Effect Antiviral and antiparkinsonian activity. 

The storage and release of DA can be modified irreversibly by reserpine (3.1), just as in vesicles containing other catecholamines and serotonin. Dopamine release can be blocked specifically by y-hydroxybutyrate (4.78) or its precursor, butyrolactone, which can cross the blood-brain barrier. High doses of amphetamines do deplete the storage vesicles, but this is not their principal mode of action. Apparently, amantadine (4.79), an antiviral drug that is likewise beneficial in parkinsonism (and also perhaps to relieve fatigue in multiple sclerosis), may also act by releasing DA. 

Amantadine, an antiviral agent, was by chance found to have antiparkinsonism properties. Its mode of action in parkinsonism is unclear, but it may potentiate dopaminergic function by influencing the synthesis, release, or reuptake of dopamine. It has been reported to antagonize the effects of adenosine at adenosine 2 receptors, which are receptors that may inhibit D2 receptor function. Release of catecholamines from peripheral stores has also been documented. 

Figure 13.8. Chemical structure of amantadine and of centrally acting anticholinergic agents used in the treatment of Parkinsonism. The antiviral compound amantadine is a dopamine-releasing agent with some anticholinergic activity.

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