Analgesia additive interaction between tadalafil and morphine in an experimental animal model

Since both morphine and tadalafil have been proven to exert some of their analgesic activity through modulation of the NO-cGMP pathway, the aim of the current study is to evaluate the pharmacologic interaction between tadalafil and morphine to decrease the dose of morphine and subsequently its side effects. The assessment was carried out through isobolographic analysis relative to ED₅₀s of both morphine and tadalafil obtained by tail-flick test on BALB/c mice. Morphine and tadalafil ED₅₀s calculated from the dose-response curves were 8303 and 2080 μg/kg, respectively. The experimental ED₅₀ values of morphine and tadalafil in their mixture were 4800 and 1210 μg/kg, respectively. Those results showed an additive interaction between morphine and tadalafil presented by a total fraction value for the mixture of 1160 μg/kg. This outcome can be interpreted by the fact that both drugs share common pathways, namely, NO-cGMP and opioid receptors. As a conclusion, the morphine and tadalafil combination showed an additive effect against acute pain, which is mediated through the central nervous system, thus providing a rationale for combining them to decrease morphine dose and thus minimizing its side effects.