Histamine H1 Antagonists/chemical synthesis; Indoles/chemical synthesis; Piperidines/chemical synthesis; Animals; Blood-Brain Barrier/metabolism; Brain/metabolism; Capillary Permeability/drug effects; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Electrocardiography/drug effects; Guinea Pigs; Half-Life; Histamine H1 Antagonists/pharmacology; Histamine H1 Antagonists/toxicity; Humans; In Vitro Techniques; Indoles/pharmacology; Indoles/toxicity; Male; Mice; Piperidines/pharmacology; Piperidines/toxicity; Radioligand Assay; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1/drug effects; Receptors, Adrenergic, alpha-1/metabolism; Receptors, Histamine H1/drug effects; Receptors, Histamine H1/metabolism; Receptors, Serotonin/drug effects; Receptors, Serotonin/metabolism; Skin/blood supply; Structure-Activity Relationship