Bethanechol and Betel Nut: Interaction Details

a) Within 3 weeks of initiating betel nut chewing, a 51-year-old Indian man experienced marked rigidity, bradykinesia, and jaw tremor. This patient had been stabilized for the previous 2 years on fluphenazine decanoate depot 50 milligrams (mg) every 3 weeks for schizophrenia and procyclidine 5 mg twice daily for a mild Parkinsonian tremor. Within one week of discontinuation of betel nut chewing, the patient's condition returned to baseline. This report appears to demonstrate decreased anticholinergic effects of procyclidine when coadministered with betel nut ¹.

b) Following betel nut ingestion, a 45-year-old Indian man developed akathisia, tremor and stiffness which was not affected by dosage escalations of up to 20 mg daily of procyclidine. This patient had been previously stabilized on fluphenthixol 60 mg depot every two weeks for the previous year for schizoaffective disorder without extrapyramidal side effects. His symptoms resolved over 4 days after discontinuing betel nut. It appears that the anticholinergic effects of procyclidine were diminished when betel nut was chewed concomitantly ¹.

c) High doses (5 mg, 10 mg, and 20 mg) of subcutaneous (SC) arecoline given one hour after SC administration of 0.5 mg of the peripheral anticholinergic agent methscopolamine increased the heart rate and blood pressure of six patients with Huntington's disease. Significant increases in blood pressure occurred at doses of 5 mg, 10 mg (p less than 0.01) and 20 mg (p less than 0.05). Heart rate increased at doses of 5 mg and 20 mg (p less than 0.01), and 10 mg (p less than 0.05). Subjective effects in some patients included tremor, flushing or pallor at the time of peak drug effect and nausea, weakness, and mental changes at the higher doses. No peripheral cholinergic effects were noted. The results indicated a central muscarinic effect for arecoline ².

d) A low dose (0.5 mg) of arecoline given intravenously 3 minutes after the peripheral anticholinergic agent glycopyrrolate 0.15 mg to 8 patients with major depressive disorder increased their heart rates. The peak heart rate increase in a non-REM portion of the sleep cycle during the 10 minute post-infusion period was 6.75 +/- 12.9 beats per minute for placebo and 25 +/- 10.3 beats per minute for arecoline. The peak heart rates all began 1 to 8 minutes after the arecoline infusion, and the mean heart rate was significantly elevated over placebo from 2 to 10 minutes after arecoline infusion (p less than 0.05) ³.

e) Though chewing betel nut alone does not significantly increase catecholamine levels, a popular betel nut preparation does. Six to eight minutes after chewing betel nut, 4 subjects had only a moderate increase in plasma noradrenaline from 266.2 +/- 105.7 picograms/milliliter (pg/mL) to 313.7 +/- 92.9 pg/mL (p equal to 0.0607). Combining betel nut with lime, catechu and Piper betel flower as is commonly done caused significant elevation of norepinephrine in nine subjects from 292.2 +/- 59.5 pg/mL to 375.1 +/- 130.0 pg/mL (p equal to 0.0244) and epinephrine from 62.5 +/- 23.9 pg/mL to 102.2 +/- 45.0 pg/mL (p equal to 0.0226). In this group dopamine was also elevated in 8 of 9 subjects, but the mean was not significant ⁴.