Peripheral Administration

Neurotoxic Potency of Peripherally Administered Acidic Excitatory Amino Acids in the Neonatal RodenV  

Structure-activity relations of the neurotoxic action of excitatory amino acids and their analogs have also been carried out in the rat striatum with direct injection of the substances (Table 5). In these studies, neurotoxicity has been monitored both by histologic analysis of Nissl-stained sections as well as by quantitative neurochemistry (Schwarcz et al., 1978  

Neurotoxic Effects of Excitatory Amino Acids Injected into the Rat Striatum  

Compound Dose (nmol) Reduction in striatal neuronal markers 

Although specific neurotoxic effects of D,L-homocysteic acid were observed at doses of 1.6 pmol, L-glutamic acid was ineffective at a dose as high as 3.4 prnol (Schwarcz et ah, 1978 ). The virtual absence of neurotoxic effects of L-glutamic acid in the adult rat striatum (Olney and deGubreff, 1977) may be due to the acute form of administration and the substantial activity of uptake and metabolic processes which rapidly reduce free levels 

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ANSWER You might, but I am not absolutely sure of that because the timecourse of the levels of the drug in brain is going to differ from those infusion paradigms, what you get with peripheral administration of the drug. 

Based on the fact that at 3 hours with a very low dose of MDMA, I saw an effect on the enzyme and no effect on the transmitter levels, we probably can t pay too much attention to that timecourse and expect to see changes that are identical to what you see in the whole animal with peripheral administration. That is what I would imagine. The experiments could be done, though. They are not that difficult. You just stick the cannulas in and infuse. 

The results of the assays for ataxia indicate that ataxia is induced by more than just an interaction with PCP receptors. The inability of metaphit to antagonize PCP-induced ataxia after peripheral administration is another indication that interactions other than with PCP receptors also mediate ataxia. 

Use uncovered plastic cannulas or a butterfly needle for peripheral administration. 

Calcium gluconate is preferred over calcium chloride for peripheral administration because the latter is more irritating to veins. 

Wan, W. et ah, Differential induction of c-Fos immunoreactivity in hypothalamus and brain stem nuclei following central and peripheral administration of endotoxin, Brain Res. Bull., 32, 581, 1993. 

The regional distribution of LSD after its peripheral administration was examined by Snyder and Reivich (109) in squirrel monkeys. They reported that... 

Similar to tobacco, lobelia may also have analgesic effects. However, it depends on the mode of administration (Damaj et al. 1997). Intrathecal lobeline produces analgesia on the tail-flick test, but subcutaneous administration is ineffective. On the other hand, subcutaneous lobeline dose-dependently enhances nicotine analgesia. Tolerance develops to this effect of lobeline after 10 days. Lobeline can also produce hyperalgesic effects when administered into the dorsal posterior mesencephalic tegmentum (Hamann and Martin 1994). However, the relevance of this to peripheral administration of lobelia is questionable because chronic injections (IP) of lobeline in rats induced no changes in tail-flick latencies (Sopranzi et al. 1991). 

Stogner KA, Holmes PV (2000) Neuropeptide-Y exerts antidepressant-like effects in the forced swim test in rats. Eur J Pharmacol 387 R9-R10 Stout SC, Owens MJ, Nemeroff CB (2002) Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment. J Pharmacol Exp Ther 300 1085-1092 StrOhle A, Jahn H, Montkowski A, Liebsch G, Boll E, Landgraf R, Holsboer F, Wiedemann K (1997) Central and peripheral administration of atriopeptin is anxiolytic in rats. Neuroendocrinology 65 210-215... 

Intracerebroventricular administration of ANP ehcited anxiolytic activity in the open field, the social interaction, and the elevated plus maze tests (Biro et al. 1999 Bhattacharya et al. 1996). The effects of central and peripheral administration of atriopeptin II, a 23 amino acid residue peptide of ANP, was furthermore investigated in the elevated plus maze test in rats previously exposed to a social defeat stress. Results show that the intracerebroventricular, intra-amygdala, and intraperitoneal administration of atriopeptin II produced anxiolytic effects without affecting spontaneous locomotor activity (Strdhle et al. 1997). 

StrOhle A, Jahn H, Montkowski A, Liebsch G, Boll E, Landgraf R, Holsboer F, Wiedemann K (1997) Central and peripheral administration of atriopeptin is anxiolytic in rats. Neuroendocrinology 65 210-215... 

Del Pozo, E., Ruiz-Garcia, C., Baeyens, J.M. Analgesic effects of diltiazem and verapamil after central and peripheral administration in the hot-plate test, Gen. Pharmac. 1990, 21, 681-685. 

Zhou, S., Bonasera, L., Carlton, S.M. Peripheral administration ofNMDA, AMPA orKA results in pain behaviors in rats, Neuroreport 1996, 7, 895-900. 

Karlsten, R., Gordh, T., Post, C. Local antinociceptive and hyperalgesic effects in in the formalin test after peripheral administration of adenosine analogues in mice, Pharmacol. Toxicol 1992, 70, 434-438. 

Additionally, cardiac function can also be modulated by centrally-located H3-receptors. The intracerebroventricular administration of (R)a-methylhistamine in conscious animals is associated with a marked reduction of the heart rate, an effect which is antagonised by thioperamide (McLeod et al., 1991). The peripheral administration of ipratropium, a muscarinic antagonist which does not cross the blood-brain barrier, prevents such inhibition, demonstrating that the activation of centrally-located histamine H3-receptors leads to an increase in the vagal tone to the heart, rather than to a facilitatory effect on the sympathetic efferent fibers. 

Matsuoka Y., Saito M., LaFrancois J., Saito M., Gaynor K., Olm V., Wang L. L., Casey E., Lu Y. F., Shiratori C., Lemere C., and DuffK. (2003). Novel therapeutic approach for the treatment of Alzheimer s disease by peripheral administration of agents with an affinity to beta-amyloid. J. Neurosci. 23 29-33. 

Animal and human clinical studies demonstrate that both endogenous and exogenous opioids can also produce opioid-mediated analgesia at sites outside the CNS. Pain associated with inflammation seems especially sensitive to these peripheral opioid actions. The identification of functional p receptors on the peripheral terminals of sensory neurons supports this hypothesis. Furthermore, activation of peripheral preceptors results in a decrease in sensory neuron activity and transmitter release. Peripheral administration of opioids, eg, into the knees of patients undergoing arthroscopic knee surgery, has shown some clinical benefit. If they can be developed, opioids selective for a peripheral site would be useful adjuncts in the treatment of inflammatory pain (see Ion Channels Novel Analgesics). Moreover, new peripherally acting dynorphins may provide a novel means to treat visceral pain. 

A unique characteristic of amphibian opioid peptides is the presence in the second N-terminal position of a D-amino acid residue that confers to these compounds high resistance against enzyme degradation. Hence amphibian opioids, unique among naturally occurring opioid peptides, can act centrally after peripheral administration. 

Opioids are known to have complex effects on body temperature in animals [46]. Depending on the receptor selectivity of an opioid, but also on several other factors such as dose, route of administration, the gender of the animal, or handling procedures, it may produce either a rise or a fall in body temperature. Biphalin, after peripheral administration in mice, produced a dose-dependent (in the range 0.1-20 mg/kg) hypothermic effect that was naloxone reversible [47]. 

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