flunarizine and Peripheral-Nervous-System-Diseases

We examined the influence of Ca++ antagonist drugs on immune response and the clinical course of experimental allergic neuritis (EAN). The Ca++ antagonists verapamil and flunarizine suppressed actively induced EAN in Lewis rats in a dose-dependent fashion when given continuously by osmotic pumps from the day of immunization. If given from onset of clinical signs, day 10 after immunization, verapamil alone had therapeutic effects. The beneficial effects of the drugs seem to be mediated primarily by an action on the autoimmune response, since in vitro lymphocyte proliferation in response to nervous tissue antigens was dose-dependently inhibited by both drugs, whereas the in vitro conductivity of demyelinated sciatic nerve was not significantly affected by the Ca++ antagonists. The suppressive effect on lymphocyte proliferation could partially be bypassed by protein kinase C activating phorbol ester alone or in combination with the Ca++ ionophore ionomycin, confirming a non-toxic effect of the Ca++ antagonists on lymphocytes.

Topics: Action Potentials; Animals; Dose-Response Relationship, Drug; Flunarizine; Lymphocyte Activation; Neuritis, Autoimmune, Experimental; Peripheral Nervous System Diseases; Rats; Rats, Inbred Lew; Sciatic Nerve; T-Lymphocytes; Verapamil