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[Fred A. Baughman Jr., MD:
looked at in this study with electron-microscope. It is probable that
similar changes are occurring in all organs, the brain included. Fred
Baughman, MD, 10/30/02]

Henderson TA, Fischer VW Effects of Methylphenidate (Ritalin) on Mammalian Myocardial Ultrastructure. The American Journal of Cardiovascular Pathology. 1994;5:68-78.

“A number of adverse reactions have been associated with MPH therapy, particularly cardiovascular side effect, such as arrhythmia, tachycardia, and changes in blood pressure [1,2]. MPH is an amphetamine congener with a molecular structure resembling that of amphiphilic drugs. Administration of certain amphiphilic drugs has been shown to induce phospholipidoses by interfering with phospholipid catabolism in a variety of cell types, resulting in a lysosomal accumulation of abnormal amounts of membranes. Ultrastructurally, one striking alteration, among others, is the presence of lamellar bodies in a variety of tissues exposed to amphiphillic drugs.”

“We have previously observed analogous lamellar membrane accumulations in myocardial cells of a patient on chronic therapy with MPH.” “In order to determine if a causal relationship exists between MPH and ultrastructural myocardial changes previously described in the patient, we administered MPH to two rodent species.

Thirty male Swiss-Webster mice, weighing approximately 25-30 g each: Groups of 3 animals each were injected (intra-peritoneal) with 0.5 mg/kg, 2.5 mg/kg or 5.0 mg /kg of Ritalin. The injections were given three times a week for periods of 4 and 14 weeks prior to sacrifice.

Results: The myocardium of mice injected with 0.5 mg/kg MPH, regardless of treatment duration, showed little or no recognizable ultrasturctural changes…Incipient alterations were observed following treatment with 1.5 mg/kg MPH for 4 weeks; however administration of this dose for 14 weeks resulted in a variety of myocardial abnormalities similar to those seen with higher doses at all time points. Initially, foci of loose, unorganized aggregates of membranes and foci of distinctly circular membranous profiles with reduplication, suggesting the formation of lamellations, were observed. These abnormalities were reminiscent of a membrane folding back on itself and spiraling inward… “Pronounced lesions in our rodents were more evident with prolonged exposure and appeared to approach a stable level of incidence; however, lesions were highly focal and a wide range of alterations within individual animals was notices. These structural abnormalities persisted to a reduced degree, for as prolonged time after stopping the MPH injections.

“…it could be argued that our results do not directly apply to the clinical situation, because MPH was administered by injection. Yet, similar pathological changes were see in the six mice that received MPH orally. The limited number of animals receiving MPH by this route dictates a cautious interpretation; nevertheless, we found no basis to expect a different pathological profile following oral administration.”

“…it is difficult to draw conclusions concerning long-term accumulation or safe doses. Yet our observations definitively showed that lesions were present in animals treated with therapeutic doses and that these lesions persisted. “

“this study, using laboratory animals under a controlled single drug regimen, corroborates and strengthens the previous supposition that MPH was a likely causal agent in the formation of similar ultrastructural alterations observed in a patient on chronic MPH therapy.”

“Our treatment protocol revealed clearly the requirement of a minimal dose, in order to induce even incipient structural changes; however, these minimum dosages fell within the range of therapeutic dosage prescribed for patients with attention deficit disorders.”

“Also noteworthy was the rapid development of pathological changes (i.e., within 3 weeks). “

“The rapid appearance of lamellar structures, coupled with the potential for irreversibility and the profound structural changes seen in a patient on long-term MPH therapy, suggests that these findings may have clinical consequences for drug interactions and long-term side effects of MPH of which clinicians should be aware. ”

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