MONOAMINE OXIDASE (MAO) INHIBITORS

Originally used for tx of tuberculosis, subsequently found to produce mood elevations. Recently discovered to be beneficial in tx of Parkinson’s disease. Non-specific effects are more pronounced so you can have high bp. Some MAO inhibitors are structurally related to amphetamine. MAO catalyzes degradation of endogenous amines.

In the CNS, two types of MAO enzymes (MAO-A and MAO-B) have been related to degradation of amines whose deficiency produces depression or Parkinson’s syndrome, respectively. Examples: tranylcypromine (Parnate), used as an antidepressant. Selegiline (L-Deprenyl), a MAO-B inhibitor, is used in the tx of Parkinson’s disease.

Serious side effects: HTN, tremors, headache, agitation, etc.; principally due to interference with degradation sympathomimetic amides that may be taken as medications, or with food or drinks. Due to side effects, the therapeutic use of MAO inhibitors is limited.

Implications for dentistry: interaction with other drugs, most notable Demerol (meperidine).

Treatment of Parkinson’s Disease:

Parkinson’s Disease is a CNS disorder manifested by slow movement, rigid muscle and trembling hands (“shaking palsy”). Related to death of specific cells in the “substantia nigra” of the CNS basal ganglia, with consequent deficiency of the neurotransmitter dopamine. Death of these cells may be due to a variety of toxic, infectious or ischemic lesions.

Control of movement by the CNS may be considered to depend on a balance of cholinergic (excitatory) and dopaminergic (inhibitory) impulses. Lack of dopamine produces imbalance and defective control of movements. Therefore, the therapeutic goal is to decrease the cholinergic influence, and/or increase the dopaminergic influence in the CNS. Anticholinergic drugs have been used, such as belladonna alkaloids, or anticholinergic-antihistaminic drugs (benztropin). Administration of L-DOPA has turned out to be more effective. While dopamine does not cross the blood brain barrier easily, DOPA can. It is then transformed into dopamine by decarboxylation in the CNS. At times DOPA is combined with decarbocxylase inhibitors (such as carbidopa) to limit its decarboxylation to dopamine in the peripheral tissues.

Category: Pharmacology Notes