The calcium channel blocker nimodipine inhibits spinal reflex pathways in humans

Voltage-sensitive calcium channels contribute to depolarization of both motor neurons and interneurons in animal studies, but less is known of their contribution to human motor control and whether blocking them has potential in future antispasmodic treatment in humans. Therefore, this study investigated the acute effect of nimodipine on the transmission of human spinal reflex pathways involved in spasticity. In a double-blinded, crossover study, we measured soleus muscle stretch reflexes and H reflexes and tibialis anterior cutaneous reflexes in 19 healthy subjects before and after nimodipine (tablet 60 mg) or baclofen (tablet 25 mg). Baclofen was used as a control to compare nimodipine's effects with known antispastic treatment. Changes in the size of the maximum H reflex (H_max)/maximum direct motor response in muscle (M_max) ratio and stretch and cutaneous reflexes following intervention with nimodipine and baclofen, respectively, were analyzed with a one-way repeated-measures (RM) ANOVA. Nimodipine significantly reduced the H_max/M_max ratio [F(2.5,42) = 15; P < 0.0001] and the normalized soleus stretch reflex [F(2.6,47) = 4.8; P = 0.0073] after administration. A similar tendency was seen after baclofen [H_max/M_max ratio: F(2.1,39) = 4.0, P = 0.024; normalized stretch reflex: F(2.8,50) = 2.4; P = 0.083]. The M_max response was unaffected by either intervention. Interestingly, during voluntary soleus activation, the stretch reflex remained unchanged with either treatment. For the cutaneous reflexes, there was a trend toward reduced early inhibition [F(1.6,9.3) = 4.5; P = 0.050] and subsequent facilitation [F(1.3,8.0) = 4.3; P = 0.065] after nimodipine. No severe adverse effects were reported after nimodipine. These findings suggest that nimodipine acutely reduced electrophysiological measures related to spasticity in healthy individuals. The effect seemed located at the spinal level, and voluntary contraction counterbalanced the reduction of the stretch reflex, highlighting its relevance for future studies on antispastic therapies.NEW & NOTEWORTHY The calcium channel antagonist nimodipine significantly reduces the size of the soleus H reflex and stretch reflex in healthy individuals without affecting maximum direct motor response (M_max) or the stretch reflex during voluntary activation. This underscores the importance of exploring nimodipine as a potential antispastic medication in the future.