Verapamil substantially increases the chemomyectomy effect of doxorubicin injected into rabbit or monkey eyelid.
Local doxorubicin injections have been used clinically to treat blepharospasm, hemifacial spasm, and other related disorders permanently and nonsurgically. Doxorubicin is an effective myotoxic agent for the removal of the orbicularis oculi muscle in the eyelid after local injection. Injections of this drug alone resulted in removal of up to 70% of the muscle fibers from the treated eyelids in monkeys. The authors attempted to optimize the conditions for doxorubicin myotoxicity of the orbicularis oculi. Doxorubicin was injected shortly after local verapamil injection in rabbits and a monkey in an attempt to maximize the muscle injury in the eyelid. Verapamil (dose, 0.5 mg or 1.6 mg in the rabbits), injected with a range of doses of doxorubicin, caused substantially increased muscle loss in the eyelid compared with doxorubicin alone. In the monkey, verapamil (dose, 0.25 mg) injection was followed by an injection of 1 mg of doxorubicin. Verapamil cotreatment resulted in increased muscle loss over that caused by doxorubicin alone in both rabbits and the monkey. Injection of verapamil alone also caused muscle loss, and this was quantified. The muscle loss with doxorubicin and verapamil injections included muscle in the preseptal portion of the muscle and even in the pretarsal muscle (which previously was difficult to destroy). This technique clinically might be used to decrease the dose of doxorubicin injected and/or decrease the total number of injections necessary but still retain a clinically effective treatment for blepharospasm and hemifacial spasm. The reduction in the dose of doxorubicin also may decrease the risk of skin injury from doxorubicin chemomyectomy in these patients.
McLoon
L K
LK
Department of Ophthalmology, University of Minnesota, Minneapolis 55455.
Ekern
M
M
Wirtschafter
J
J
D000818:Animals; D002452:Cell Count; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D005143:Eyelids / Q000187:drug effects* / Q000473:pathology; D008252:Macaca fascicularis; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology*
D004317:Doxorubicin; D014700:Verapamil