Pheromones enhance somatosensory processing in newt brains through a vasotocin-dependent mechanism.

We tested whether the sex pheromones that stimulate courtship clasping in male roughskin newts do so, at least in part, by amplifying the somatosensory signals that directly trigger the motor pattern associated with clasping and, if so, whether that amplification is dependent on endogenous vasotocin (VT). Female olfactory stimuli increased the number of action potentials recorded in the medulla of males in response to tactile stimulation of the cloaca, which triggers the clasp motor reflex, as well as to tactile stimulation of the snout and hindlimb. That enhancement was blocked by exposing the medulla to a V1a receptor antagonist before pheromone exposure. However, the antagonist did not affect medullary responses to tactile stimuli in the absence of pheromone exposure, suggesting that pheromones amplify somatosensory signals by inducing endogenous VT release. The ability of VT to couple sensory systems together in response to social stimulation could allow this peptide to induce variable behavioural outcomes, depending on the immediate context of the social interaction and thus on the nature of the associated stimuli that are amplified. If widespread in vertebrates, this mechanism could account for some of the behavioural variability associated with this and related peptides both within and across species.

Rational design of anticonvulsants: a quantum pharmacologic study of the ion channel-modulating FMRFamide tetrapeptide as an endogenous anticonvulsant.

We applied the computational techniques of quantum pharmacology to examine molecular conformations (shapes and geometries) of the tetrapeptide FMR-Famide (L-Phe-L-Met-L-Arg-L-Phe-NH2), determining the geometric features necessary for anticonvulsant activity. The rigorous tiered hierarchical approach used molecular mechanics, molecular dynamics, and semiempirical quantum mechanics calculational methods. Low-energy conformations showed pertinent conformational information to be considered in the rational design of novel anticonvulsants. The FMRFamide peptide backbone assumes a bent but primary planar geometry. Distinct polar and nonpolar regions are created as the two Phe residues occupy one "face" of the bent conformation, while the Met and Arg residues occupy the opposite face. The aromatic rings point away from each other along the backbone, and this separation is consistent among the low-energy conformations at approximately 11-12 A. The Met side chain interacts with neither the peptide backbone nor the side chains of other residues. Molecular mechanics and semiempirical quantum mechanics calculations predict limited variation in the orientation of the Arg side chain.

Mechanisms of post-traumatic seizures: a quantum pharmacological analysis of the molecular properties of an epileptogenic focus following iron-induced membrane peroxidation.

Late post-traumatic epilepsy following severe head trauma has been well documented. While there is increasing evidence suggesting that iron-induced lipid peroxidation of neural membranes may accompany cerebral haemorrhage, the pathogenic processes of post-traumatic epileptogenesis remain unknown. Furthermore, the effective prophylactic use of standard anticonvulsant drugs is unsubstantiated. The rational design of therapeutic agents specific for the prevention and treatment of post-traumatic epilepsy hinges on understanding the molecular membrane events at the epileptogenic focus. This study employs the techniques of theoretical quantum pharmacology to provide a structural analysis of neural phospholipid membranes, investigating changes in membrane integrity at the epileptogenic focus as the molecular basis for seizure activity. Molecular mechanics calculations and molecular dynamics simulations were used to model the biochemical events of the epileptogenic focus. We predict that applications of quantum pharmacological techniques to model biochemical events may provide an understanding of proconvulsive pathogenic mechanisms in post-traumatic epilepsy.