Benzodiazepines (BDZs) and non-BDZ drugs are associated with side effects such as headaches, dizziness, and palpitations. Therefore, we evaluated whether these drugs have direct vasorelaxation effects onphenylephrine-contracted arteries isolated from Wistar rats using myography. The binding assay of the drugs for GABA_Areceptors in rat brain was performed using [3H]flunitrazepam as an agonist. 
Zolpidem caused over 80% relaxation at a concentration of 10 μM in the thoracic aorta; diazepam, estazolam, etizolam, and tofisopam caused 60−70% relaxation, whereas alprazolam, bromazepam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, loflazepate, flunitrazepam, flurazepam, lorazepam, lormetazepam, midazolam, nimetazepam, nitrazepam, oxazepam, temazepam, triazolam, and zaleplon caused less than 50% relaxation. No correlation was observed between the GABA_Areceptor binding affinity of the 23 drugs excluding tofisopam which had little binding affinity, and vascular relaxation.
The study demonstrated that many BDZs and non-BDZ drugs cause vasorelaxation. GABA_Areceptor activation may not be mainly associated with vasorelaxation. The direct vasodilatory effects of these drugs may be partly involved in the mechanisms underlying their side effects.