Pharmacology of Parkinson's disease and amyotropic lateral sclerosis. Parkinson's disease and amyotrophic lateral sclerosis are progressive neurodegenerative diseases of unknown etiopathogenesis. Akinesia, muscle rigidity and resting tremor are characteristic symptoms of Parkinson's disease. Degeneration of dopaminergic nigrostriatal neurons of the substantia nigra pars compacta and the resulting loss of dopamine in the striatum are the primary cause of this disease. No neuroprotective therapy slowing down the progress of the disease has been found, so far. Only symptomatologic treatment is available. L-DOPA, a precursor of dopamine which is transformed to dopamine by aromatic amino acid decarboxylase (AADC) is the best antiparkinsonian medication. This drug is applied jointly with peripheral AADC (carbidopa, benserazide), MAO-B (deprenyl), or COMT (entacapon. tolcapon) inhibitors. Dopaminergic transmission may also be restored by agonists of postsynaptic dopamine D2 and D3 receptors: bromocriptine, lisuride, pergolide, cabergoline, pramipexole, or ropinirole. Drugs which inhibit overactive cholinergic and glutamatergic systems include: non-selective antagonists of muscarinic cholinergic receptors (benztropine, trihexyphenidyl, biperiden), and amantadine ń an NMDA receptor antagonist. A new compound istradefylline, a selective antagonist of adenosine A2A receptors is now in phase III clinical trials. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disease which results in a loss of motoneurons in the ventral horn of the spinal cord (lower motoneuron) and in the motor cortex (upper motoneuron). The disease is characterized by progressive muscle weakness, muscle atrophy and paralysis, leading to death due to respiratory failure after 3 years on the average. Amongst a great number of medications under development, only riluzole was approved for human therapy. This drug reduces glutamatergic transmission by: (1) inhbition of glutamate and glycine release, (2) inhibition of the voltage-dependent sodium channels, (3) non-competitive blockade of NMDA receptors. However, its efficiency is limited because of the lack of influence on muscle force of patients and short-term prolongation of their lives (ca. 3 months).