Sven Korte

High Definition Oscillometry: a novel technique for non-invasive blood pressure monitoring in the cynomolgus monkey (Macaca fascicularis)

Background  Current approaches for accurate blood pressure determination rely predominantly on invasive techniques. High Definition Oscillometry (HDO) was evaluated as a potential non‐invasive approach for accurate blood pressure recordings in cynomolgus monkeys.

Differential responses to JNJ‐37822681, a specific and fast dissociating dopamine D2 receptor antagonist, in cynomolgus monkey and Sprague–Dawley rat general toxicology studies: clinical observations, prolactin levels, mammary histopathology findings and toxicokinetics

JNJ‐37822681 is a potent, specific and fast dissociating dopamine D2 receptor antagonist intended for the treatment of schizophrenia. Its nonclinical toxicological profile was investigated in a series of general repeat dose toxicity studies in cynomolgus monkeys and Sprague–Dawley rats. The maximum duration of treatment was 9 and 6 months, respectively. Interspecies differences were noted in the response to JNJ‐37822681 in terms of extrapyramidal (EPS)‐like clinical signs and prolactin‐mediated tissue changes in the mammary gland. Monkeys showed severe EPS‐like clinical signs such as abnormal posture, abnormal eye movements and hallucination‐like behavior at relatively low exposures compared to those associated with EPS in patients with schizophrenia. The high sensitivity of the monkey to JNJ‐37822681‐induced EPS‐like signs was unexpected based on the fast dissociating properties of the compound. Rats, however, were not prone to EPS. Elevated serum prolactin levels were found in rats and monkeys. While rats showed slight to moderate prolactin‐related tissue changes upon histopathological examination in all studies, which among others affected the mammary gland, only minor mammary gland tissue changes were noted in monkeys. Prolactin levels were only slightly increased in patients with schizophrenia receiving relatively high dose levels of JNJ‐37822681. The monkey toxicology studies did not provide an exposure‐based safety margin, while in rats adverse effects were only noted at exposures considerably higher than those achieved at efficacious plasma concentrations in the clinic. Overall, the available data suggest that the cynomolgus monkey showed better predictivity towards the nature of JNJ‐37822681‐associated adverse events in humans than the Sprague–Dawley rat. Copyright

Basic Physiology of Callithrix jacchus

The common marmoset, a unique South American New World monkey species, is widespread in laboratory settings and in zoological gardens. In recent years, common marmosets have become a suitable animal model in many research fields. Their small size, easy handling and husbandry, early sexual maturity, and short gestation makes them attractive for toxicology and reproductive biology. Important distinctions from other primate species regarding nutrition, reproduction, and development exist, and this knowledge is essential for successful husbandry breeding and study design. This chapter provides an overview of important aspects of the basic physiology of the common marmoset.

Considering the Use of Callithrix jacchus

Abstract In this chapter we review the data available on the use of marmosets as a valuable NHP model and report on histopathological specificities in a variety of organs. Based on the differences described, the marmoset model is discussed in the context of toxicological safety assessments as well as a model for general research on the pathophysiology of human diseases.