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Tics

Published: 2020
SYNOPSIS

There is a physiological effect of thimerosal in humans that could alter dopamine receptor pathways which are associated with locomotion and more importantly, motor disorders.

TITLE

The activities of drug inactive ingredients on biological targets

CITATION

Joshua Pottel, et al.; The activities of drug inactive ingredients on biological targets;July 24, 2020; Science Vol. 369, No. 6502; DOI: 10.1126/science.aaz9906.

SUMMARY

Excipients, considered “inactive ingredients,” are a major component of formulated drugs and play key roles in their pharmacokinetics. Despite their pervasiveness, whether they are active on any targets has not been systematically explored. We computed the likelihood that approved excipients would bind to molecular targets. Testing in vitro revealed 25 excipient activities, ranging from low-nanomolar to high-micromolar concentration. Another 109 activities were identified by testing against clinical safety targets. In cellular models, five excipients had fingerprints predictive of system-level toxicity. Exposures of seven excipients were investigated, and in certain populations, two of these may reach levels of in vitro target potency, including brain and gut exposure of thimerosal and its major metabolite, which had dopamine D3 receptor dissociation constant Kd values of 320 and 210 nM, respectively. Although most excipients deserve their status as inert, many approved excipients may directly modulate physiologically relevant targets.

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Published: 1953
SYNOPSIS

Aluminum caused tics and grand mal seizures in monkeys.

TITLE

Experimental Epilepsy in the Monkey Following Multiple Intracerebral Injections of Alumina Cream

CITATION

Joseph G. Chusid, Lenore M. Kopeloff, Ph.D. and Nicholas Kopeloff, Ph.D. The Bulletin, 1953.

SUMMARY

The multiple intracerebral injection of alumina cream (aluminum hydroxide cream) into a principal cerebral sensorimotor cortical area is effective in producing chronic epilepsy in monkeys. In all injected animals a variable degree of contralateral hemiparesis was obvious immediately after operation. In five of the six monkeys injected unilaterally, spontaneous contralateral focal motor seizures were evident three to four weeks after operation. Initially there occurred almost continuous twitch-like movements of varying amplitude and regularity, involving the musculature of the contralateral face and limbs. Excitement, agitation, movement or stress readily aggravated and accentuated this type of motor activity and sometimes led to Jacksonian spread with full-blown generalized convulsive seizure and exhaustion.

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