Transient global amnesia after intake of tadalafil, a PDE-5 inhibitor: a possible association?

Abstract

Inhibitors of phosphodiesterase type 5 (PDE-5) are well established as an oral treatment for the majority of patients with erectile dysfunction (ED). PDE-5 is found in high concentration in smooth muscle cells of the corpora cavernosa. However, enzymes of the PDE family are also expressed in various other tissues, including the brain. Little is known about its effects on the central nervous system (CNS), although it has been suggested that PDE-5 inhibitors might cross the blood-brain barrier. Side effects, such as headache, nasal congestion, flushing, nausea, are much more common. We describe a patient who had a transient global amnesia (TGA) after his first-ever use of tadalafil, a potent PDE-5 inhibitor. Despite the fact that the aetiology of TGA has not entirely been clarified at present, we consider the hypothesis of a causal relationship as tempting with respect to the current hypotheses of TGA pathophysiology. This case, together with others, suggests that PDE-5 inhibitors might be capable of exerting adverse effects in the CNS. Physicians should be aware of the possibility of neurological disturbances when prescribing PDE-5 inhibitors for ED.

Tadalafil enhances working memory, and reduces hippocampal oxidative stress in both young and aged mice

“…Phosphodiesterase (PDE) inhibitors may work as cognitive enhancers due to their expression of phosphodiesterases in the central nervous system (CNS) (Menniti et al, 2006). Tadalafil (CAS number 171596-29-5) is a potential phosphodiesterase 5 (PDE-5) inhibitor (Schiefer and Sparing, 2005), which has been used to treat erectile dysfunction (Donatucci et al, 2008;Porst et al, 2009). It can cross the blood brain barrier (Garcia- Barroso et al, 2013).…”

Two Cases of Delayed-onset Transient Global Amnesia After Saline-contrast Transthoracic Echocardiography

“…1,5,6 Echocardiogram has also previously been reported as a trigger, both with 7 and without 8 agitated saline contrast. These include seizure activity, paradoxical emboli causing transient cerebral dysfunction, migraine-related cortical spreading depression, and transient cerebral ischemia resulting from venous congestion.…”

The phosphodiesterases type 5 inhibitor tadalafil reduces the activation of the hypothalamus-pituitary-adrenal axis in men during cycle ergometric exercise

“…Because of the absence of modifications in metabolic parameters between the placebo and tadalafil group (e.g., lactate production, O 2 consumption), we hypothesize that tadalafil, after crossing the blood-brain barrier (49,55), first reduced the ACTH activation by influencing NO-mediated pathways (see Introduction) in the central nervous system (CNS). Probably, tadalafil affected ACTH secretion by inhibiting the PDE5 expressed in CNS (32), thus enhancing cGMP-mediated effects of NO on the hypothalamus-pituitary axis.…”