title: Cerebral haemodynamic response or excitability is not affected by sildenafil.
abstract: Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70.3+/-6.6 kg), the effect of sildenafil on a visual (reversing checkerboard) and a hypercapnic (6% CO2 inhalation) response was evaluated using functional magnetic resonance imaging (fMRI, 3 T MR scanner). On separate occasions, visual-evoked potential (VEP) measurements (latency (P100) and maximal amplitude) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100 mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication is that sildenafil-induced headache does not include a general lowering of threshold for a neuronal or cerebrovascular response, and that sildenafil does not modulate the hypercapnic response in healthy subjects.
authors.affiliation: Department of Neurology, Copenhagen University Hospital, Glostrup, Denmark. ckruuse@dadlnet.dk
authors.forename: Christina
authors.initials: C
authors.lastname: Kruuse
authors.forename: Adam E
authors.initials: AE
authors.lastname: Hansen
authors.forename: Henrik B W
authors.initials: HB
authors.lastname: Larsson
authors.forename: Martin
authors.initials: M
authors.lastname: Lauritzen
authors.forename: Egill
authors.initials: E
authors.lastname: Rostrup
mesh_terms: D000328:Adult; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005074:Evoked Potentials, Visual; D005260:Female; D006261:Headache / Q000139:chemically induced*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006935:Hypercapnia; D008279:Magnetic Resonance Imaging; D010775:Photic Stimulation; D010879:Piperazines / Q000009:adverse effects*; D011687:Purines / Q000009:adverse effects; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate