We introduce a framework for efficient Markov chain Monte Carlo algorithms targeting discrete-valued high-dimensional distributions, such as posterior distributions in Bayesian variable selection problems. We show that many recently introduced algorithms, such as the locally informed sampler of Zanella (J Am Stat Assoc 115(530):852–865, 2020), the locally informed with thresholded proposal of Zhou et al. (Dimension-free mixing for high-dimensional Bayesian variable selection, 2021) and the adaptively scaled individual adaptation sampler of Griffin et al. (Biometrika 108(1):53–69, 2021), can be viewed as particular cases within the framework. We then describe a novel algorithm, the adaptive random neighbourhood informed sampler, which combines ideas from these existing approaches. We show using several examples of both real and simulated data-sets that a computationally efficient point-wise implementation (PARNI) provides more reliable inferences on a range of variable selection problems, particularly in the very large p setting.