Monoamine oxidase inhibitors and L-dopa.

Abstract

The increasing use of L-dopa in the treatment of Parkinsonism has drawn attention to the way in which this catecholamine precursor may interact with other drugs commonly given to such patients. It was reported (Degkwitz et al., 1960) that a monoamine oxidase (M.A.O.) inhibitor potentiated the pressor effect of intravenous L-dopa in psychiatric patients, and a similar effect has been shown in Parkinsonian patients given L-dopa by mouth (Barbeau et al., 1962). In view of the large doses of L-dopa now being given to Parkinsonian patients, many of whom are depressed, we felt that it was important to assess the degree of risk from combination therapy with M.A.O. inhibitors and to study how the hypertension could be controlled. days the effect of oral L-dopa was observed by using techniques previouslv described (Elis et al., 1967).The effect of 50 mg. L-dopa on the patient's blood pressure and pulse rate is shown in the Chart. When the systolic pressure reached 180 mm. Hg an a-adrenoreceptor blocker, phentolamine, was given intravenously. Satisfactory control was achieved with a total dose of 9 mg. During this study no alteration was seen in the electrocardiogram, but 45 minutes after the administration of L-dopa the patient reported that his limbs felt "much looser," and clinical assessment confirmed a definite reduction in the degree of rigidity at the wrists. This effect lasted for five minutes. There was no alteration in the Parkinsonian tremor at this time.Next day the experiment was repeated, using 25 mg. L-dopa, but no change in blood pressure, pulse rate, electrocardiogram, or rigidity was seen with this dose.Three weeks after the M.A.O. inhibitor had been discontinued single doses up to 500 mg. of L-dopa produced no effect on the patient's blood pressure. COMMENTThese results confirm that a dose of L-dopa which normally produces no effect on the blood pressure can cause a dramatic rise when given to a Parkinsonian patient taking phenelzine. The extent of this rise is related to the dose of Ldopa. Our results are similar to those obtained with tranylcypromine (Barbeau et al., 1962) and isocarboxazid (Birkmayer and Hornykiewicz, 1962 Though the exact mechanism by which the combination raises the blood pressure is not clear, it has been shown that an a -adrenoreceptor blocker controls this hypertension in non-Parkinsonian patients (Hodge et al., 1964). Catecholamine metabolism is abnormal in patients with idiopathic Parkinsonism (Goodall and Alton, 1969); nevertheless, our results suggest that intravenous phentolamine is effective treatment of hypertensive crises due to L-dopa in such patients. We recommend that management in such cases should follow the principles recently outlined by Simmons et al. (1970).An interesting feature in our patient was the absence of any change in pulse rate when the blood pressure rose. This is compatible with the increased blood pressure being caused by dopamine rather than by noradrenaline or adrenaline (Horowitz et al., 1962). It is unlikely that the benzhexol therapy had suffic...

Psychotropic and Medical Drug Interactions

“…Ten days later, levodopa 50 mg was aded orally. Blood pres sure changed from 140/90 to 200/120 mm [144], This has been confirmed by another similar report [147], Chlordiazepoxide ad ministered to a parkinsonian patient stabi lized on levodopa has been reported to have markedly reduced the levodopa effect. Dis continuation of chlordiazepoxide brought parkinsonism under control [148], Phenothiazines [149.…”

The possible mechanisms of action of (-)deprenyl in Parkinson's disease

“…As the majority of parkinsonian patients treated with levodopa experience more or less troublesome side effects, any effective levodopa-sparing mechanism is of high practical importance. Clinical studies revealed, however, that the nonselective MAO-inhibitors, in clinical use at present, are definitely contraindicated in patients taking levodopa because hypertensive crises may result (Hunter et al, 1970). It is even recommended to withdraw an MAO inhibitor a month prior to levodopa administration (cf.…”

“…At present the use of MAO inhibit0rs is considered to be definitely contraindicated in parkinsonian patients treated with levodopa, because hypertension may result (cf. Hunter et al, 1970).…”

L-DOPA inhibits nitric oxide-dependent vasorelaxation via production of reactive oxygen species in rat aorta

“…MAO-A/B mixed inhibitors may be efficacious in the inhibition of dopamine metabolism and the treatment of PD (30,32), but there are some side effects of increasing the blood pressure in the presence of a non-selective monoamine oxidase (MAO)-A/B inhibitor or a selective MAO-A inhibitor, L-DOPA increased blood pressure in both PD patients and rats (4,33). These results indicate that L-DOPA exerts directly on its vasoconstrictive effect without conversion to dopamine.…”