Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

The Effect of Depressive Symptoms on Adherence to Daily Oral PrEP in Men who have Sex with Men and Transgender Women: A Marginal Structural Model Analysis of The iPrEx OLE Study

We assessed the role of depressive symptoms on adherence to daily oral FTC/TDF for HIV PrEP in cisgender men who have sex with men (MSM) and transgender women who have sex with men (TGW) using data from the iPrEx OLE study. A marginal structural logistic regression model was used to estimate the effect of time-varying CES-D scores on having protective levels of drug concentration, adjusting for confounding by sexual practices over time, prior adherence, and baseline demographic characteristics. We found a non-monotonic relationship between CES-D score and odds of protective FTC/TDF levels in MSM. We found evidence that the effect of depression on adherence varied between MSM and TGW, and that depressive symptoms did not contribute greatly to decreased adherence on a population scale. We recommend that depressive symptoms not preclude the prescription of PrEP, and that MSM and TGW be studied separately