The anabolic effect of combining salbutamol with L-dopa

Ten years ago neurologists at the University of Arkansas published in Clinical Neuropharmacology the results of a small study, which may or may not be of interest to our dear readers. Nor do we know for sure whether salbutamol and L-dopa – the combination that the neurologists tested in the study – is completely safe. What we do know is that the anabolic effects that the researchers observed are remarkable.

Ten years ago neurologists at the University of Arkansas published in Clinical Neuropharmacology the results of a small study, which may or may not be of interest to our dear readers. Nor do we know for sure whether salbutamol and L-dopa – the combination that the neurologists tested in the study – is completely safe. What we do know is that the anabolic effects that the researchers observed are remarkable.

The eight people who served as subjects for the neurologists’ experiment all suffered from Parkinson’s and had an average age of 59. They were already taking L-dopa, an amino acid that boosts the production of dopamine in the brain. The body’s production of dopamine declines rapidly with the onset of Parkinson’s and as a result brain cells lose their function. L-Dopa supplementation reduces the symptoms in the first stage of the disease.

The average L-dopa dose of the subjects was 481 mg per day.

Cells absorb more L-dopa, and therefore also produce more dopamine, when they are exposed to adreno-beta-2-agonists. [Am J Physiol Renal Physiol. 2000 Jul;279(1):F77-83.] Animal studies have shown that adreno-beta-2-agonists improve the brain’s uptake of L-dopa. [Eur J Pharmacol. 1992 May 14;215(2-3):245-51.]

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That’s why the researchers wanted to try the combination of salbutamol, a mild adreno-beta-2-agonist, and L-dopa, to see what effect it would have on their patients. They gave their subjects 4 oral doses of 4 mg salbutamol daily.

In one sixty-year-old patient the salbutamol/L-dopa combination caused headache, restlessness and trembling. She stopped taking the combo after two weeks. The other subjects continued for 14 weeks. During this period they also did strength training twice a week.

The table below shows that the subjects’ maximal strength increased by a modest amount and that their body composition changed considerably. While there was no change in the subjects’ bodyweight, their lean body mass increased by 7.7 kg.

Ooh la la.

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Don’t take any notice of the weight that the subjects lifted with the chest press. No doubt there’s an editorial error there.

In half of the patients the addition of salbutamol to the L-dopa medication reduced the symptoms of the Parkinson’s.

The researchers emphasise that they don’t know whether the combination they tested is safe.

“The observed significant increase in the mean heart rate, seen in ten percent of patients using salbutamol, and the isolated case reports of cardiac arrhythmias and angina underscore the need for careful cardiac evaluation when use of salbutamol is considered”, they write. “The central nervous system side effects include enhanced physiologic tremor (twenty percent), insomnia, dizziness, drowsiness, restlessness, irritability, nervousness, visual hallucinations, and headache.”

Albuterol improves response to levodopa and increases skeletal muscle mass in patients with fluctuating Parkinson disease.

Uc EY, Lambert CP, Harik SI, Rodnitzky RL, Evans WJ.

Source

Department of Neurology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. ergun-uc@uiowa.edu

Abstract

Animal studies indicate that beta(2)-adrenergic receptor agonists enhance transport of levodopa across the blood-brain barrier. Preliminary studies showed improved response to levodopa in patients with Parkinson disease (PD) who were given albuterol as adjunctive therapy. Beta(2)-adrenergic agonists may offer additional benefits to PD patients via their skeletal muscle anabolic effects, particularly those who experience decreased muscle strength and weight loss. Nondemented, fluctuating PD patients receiving levodopa but not experiencing severe dyskinesias underwent the following tests at baseline and 14 weeks after treatment with albuterol sulfate (4 mg four times a day, orally): Unified Parkinson’s Disease Rating Scale motor, tapping, and stand-walk-sit tests every 30 minutes between 8 am and 5 pm; body composition analyses using whole-body plethysmography and computed tomography of the thigh; muscle strength tests; and the Parkinson’s Disease Questionnaire (PDQ-39). Results were analyzed using paired t-tests (2 tailed), repeated-measures analysis of variance, and the Wilcoxon signed-rank test. Seven of 8 enrolled patients completed the study; 1 patient withdrew because of headache and anxiety. The area under the curve for all-day UPDRS motor scores improved by 9.8 +/- 9.1% (mean +/- standard deviation; P < 0.05) and tapping improved by 7.6 +/- 8.1% (P < 0.05). The effect was more pronounced when only the response to the first levodopa dose (area under the curve, 8-11 am) was analyzed: 13.0 +/- 9.8% and 9.8 +/- 9.6% respectively. Thigh muscle cross-sectional area increased significantly as measured by computed tomography (5.3 +/- 3.2%, P < 0.01), as did fat-free mass by whole-body plethysmography combined with total-body water determination (9.5 +/- 2.9%, P < 0.05). There was no significant improvement in the stand-walk-sit test, muscle strength tests, other UPDRS sections, daily OFF time, or PDQ-39. Four patients were rated as having a mild global improvement (+1 point) on a -3 to +3-point scale, and 3 of them chose to continue albuterol beyond the termination of the study. The mean heart rate increased from 78.3 +/- 9.3 beats/minute to 85.6 +/- 8.7 beats/minute (P < 0.05). No laboratory abnormalities or electrocardiographic changes were induced by albuterol in any subject. This open-label pilot study suggests that albuterol increases muscle mass and improves the therapeutic response to levodopa in patients with fluctuating PD. A double-blind, placebo-controlled study is needed to confirm the effects and safety profile of beta(2)-agonists in PD. PMID: 12897642 [PubMed - indexed for MEDLINE] Source: http://www.ncbi.nlm.nih.gov/pubmed/12897642  
  

 

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