Neurophysiological and biochemical research on neuroleptics have led to a better understanding of how haloperidol cause many of their adverse effects and possibly their therapeutic effects. Neuroleptics have effects at many different site in the nerve system, including dopamine receptor that macro molecules on the outside surface of platelet cells which recognize catecholamine. Stimulation of these reptors leads to biological changes within cell and antagonism by a prevents the changes. Haloperidol were kown to antagonize but not to stimulate many dopamine receptor, it´s affinity, and adenylate energy charge. How tightly a drug binds to a dopamine receptor was measured terms of affinity, and the affinity of a neuroleptic for dopamine receptor may be predictive of likelyhood, that the drug will cause certain adverse effects in shizophrenic patients.
To investigation the antagonist action in dopamine turnover and it´s receptor function and adenylate energy charge dependent nucleotide metabolism by haloperidol. In the platelet membrane of normal human and schizophrenic patients, rat striatum, catecholamine and dopamine receptor and adenylate energy charge was measured.
The results were as follows.
1. In plasma catecholamine of normal human norepinephrine concentration was 407 ± 247.5pg/ml, epinephrine concetration was 250±98.2 pg/ml, dopamine concentration was 36± 14.2 pg/ml. 2. Dopamine receptor and it´s affinity in normal human platelet membrane was 60.9 ±51.8 fmol/mg of protein, 7.5-1=6.01 nmoI and adenylate energy charge was 0.63±
0.08.
3. Dopamine receptor and it´s affinity in schizophrenic patients platelet membranes was 110.61±58.88 fmol/mg of protein, 8.5±6.69 nmol, and norepinephrine was 182 139.6 pg/ml, and epinephrine was 123±45.1 pg/ml, and dopamine was 98.3± 18.2 pg/ml, and adenylate energy charge was 0.64±0.12.
4. In medication with 5mg per kg of haloperidol, dopmine of the rat striaum reduced from 810±20.8pg/ml to 492±35.2 pg/ml, and adenylate energy charge changed from 0.83±0.06 to 0.84±0.09. Dopamine receptor in the rat striatum reduced from 341± 11.3 fmol/mg of protein to 322±9.2 fmol/mg of protein and it´s affinity increased from 2.2±0.61 nmol to 2.6±0.52 nmol,adenylate energy charge increased from 0.83
±0.06 to 0.84±0.09.
5. In oral medication with 20 mg per day on the 10 days in 23 schizoprenic patients, dopamine in serum reduced from 98.3± 18.2 pg/ml to 41.2±8.7 pg/ml. Dopamine receptor in the platelet membranes of schizophrenic patients reduced from 110.6±58.9 fmol/mg of protein to 102.3±31.2fmol/mg of protein and it´s affinity in the pletelet membrane increased 8.5±6.69 nmol to 8.9±3.26 nmol and adenylate energy charge increased from 0.65±0.12 to 0.67±0.11.
The results were suggested that haloperidol could reduced dopamine and dopamine receptor by antagonist action against dopamine receptor in schizophrenic patients and so it could control adenylate energy charge by nucleotide metabolism.
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