Ifenprodil (IFEN) is marketed as Vadilex® for the treatment of transient ischaemic attack and generalised symptoms of mental deterioration related to cerebrovascular insufficiency (Boyce et al. 1999). It was further shown however that IFEN acts as an NMDA_2B, 5HT₂, 5-HT_1A, L-type Ca ²⁺ and ₁ adrenoceptor antagonist (Boyce et al., 1999).

Previous studies have shown that ifenprodil impairs motor coordination in the rotarod. Concurrent administration of verapamil with IFEN the fall time was significantly reduced compared to IFEN alone (Maginn, 2003). The aim of this study was to examine the 5-HT₂ involvement in the IFEN effect on rotarod performance by co-administering IFEN with mianserin (5HT₂ antagonist) in rats and testing rotarod performance.

To determine the effects of IFEN and mianserin on motor co-ordination, male Sprague Dawley rats (180-200 g, Møllegård & Bomholdtgård A/S, Denmark) were first trained as outlined by Maginn (2003). On the day of testing the animals were then randomised into separate groups to receive either IFEN (20 mg/kg) or saline vehicle (dose volume 5 ml/kg). IFEN was administered intraperitoneally 60 min prior to testing and mianserin 5.0, 25.0 and 50.0 mg/kg (dose volume 5 ml/kg) was administered intraperitoneally 30 min prior to testing. The animals were placed on the accelerating rotarod (increasing from 4 to 40 r.p.m. during a 5 min period) and the time for which the rats were able to remain on the rotarod was recorded. The results are expressed as time (sec) on the wheel.The results are shown in Table 1:

**p<0.001 vs vehicle, #p<0.05 vs IFEN 20 mg/kg + mianserin 25 mg/kg (One way ANOVA followed by Newman-Keuls multiple comparison test).

Mianserin alone did not significantly effect the rotarod performance in rats. The highest dose of mianserin when administered concomitantly with IFEN significantly decreased time on the wheel when compared to the low dose of mianserin when administered concomitantly with ifenprodil.

The mechanism by which the higher mianserin dose further impaired the motor coordination is unclear. It is known that 5-HT2 receptors modify the serotonin levels in the prefrontal cortex (Brocco et al., 2002). Increasing serotonin levels may modulate mood, nociception and mnesic function all of which could modulate motor behaviour (Brocco et al., 2002).

Brocco M., Dekeyne, A., Veige, S., et al., (2002) Pharm. Biochem. Behaviour 71:667-680.
Boyce S, Wyatt A, Webb JK, et al., (1999) Neuropharmacology, 38(5):611-623.
Maginn M. (2003) PA2online, 1(2), 065P.