Pharmacological challenge

COMMENT Just a very brief comment that originally followed up on the idea of pharmacologic challenge. It is a very powerful technique with which one can detect underlying or covert neurochemical deficits. 

It may be that any peripherally adversive stimulus — especially one that stimulates sympathetic activity — thus has the potential to activate brain areas of prime importance in the formation of anxiety symptoms. As a result of pharmacological challenge studies, biochemical assays, neuroimaging and studies of animal models, a number of centrally acting neurotransmitters, and their relevant neural circuits, are implicated in anxiety. These neurotransmitters include norepinephrine, serotonin, GABA, neuropeptide Y, cholecystokin and substance P. 

Taken together, so far, pharmacologic challenge studies involving 5-HT have been similarly unable to establish a primary role for 5-HT in the pathophysiology in panic disorder (Charney and Drevets 2002). 

Barr, L.C., Goodman, W.K., Price, L. H., McDougle, C.J. and Char-ney, D.S. (1992) The serotonin hypothesis of obsessive compulsive disorder implications of pharmacologic challenge studies. / Clin Psychiatry 53(4, Suppl) 17-28. 

As yet, few attempts have been made to study the effects of pharmacological challenge in individual primates that have been socially stressed or that are temperamentally vulnerable. The success of this approach is illustrated by an important study (Insel et al. 1988) in which peer-reared rhesus monkeys were shown to be especially sensitive to a p-CCE challenge and by our own studies using a behavioral test battery as a screening instrument to identify vulnerable and resistant subjects before administration of CCK-4 (Palmour et al. 1992a). 

Barr LC, Goodman WK, Price LH, et al The serotonin hypothesis of OCD implications of pharmacologic challenge studies. J Chn Psychiatry 4 17-28s, 1992 Barr LC, Goodman WK, Price LH The serotonin hypothesis of obsessive compulsive disorder. Int Clin Psychopharmacol 8 (suppl 2 79-82, 1993 Barr LC, Goodman WK, McDougle CJ, et al Tryptophan depletion in patients with OCD who respond to serotonin reuptake inhibitors. Arch Gen Psychiatry 51 309-17, 1994... 

Given that the seat of hormonal modulation is in the limbic-hypothalamic-pituitary axis, endocrine changes serve as important correlates to major psychiatric disorders. These changes include basal hormone concentrations, as well as responses to pharmacological challenges. Equally important, endocrine disorders may present with psychiatric symptoms (e.g., manic symptoms in hyperthyroidism, severe depression in hypercortisol ism, psychotic symptoms associated with Cushing s syndrome). Commonly used neuroendocrine tests include the following. 

Bloom SR et al The obesity epidemic pharmacological challenges. Molec Interventions 2008 8 82. [PMID 18403653]... 

Aldose reductase inhibitors Structure-activity relationships and therapeutic potential, 18, 139 Alzheimer s Disease A pharmacological challenge, 25, 203 Amantadine, 8, 11... 

There is evidence from PET studies of reduced 5HT1A receptors in aggressive individuals as measured using pharmacological challenges (Coccaro et al., 1990 Cleare and Bond, 2000). Moreover, serotonin transporter availability is reduced in the anterior cingulate in patients with impulsive aggression relative to age- and sex-matched controls (Frankie et al., 2005). 

Patients with orthostatic hypotension (excessive fall in blood pressure with standing) often represent a pharmacological challenge. There are diverse causes for this disorder, including the Shy-Drager syndrome and idiopathic autonomic failure. Therapeutic approaches include physical... 

Nelson DL. The serotonin2 (5-HT2) subfamily of receptors pharmacological challenges. Med Chem Res 1993 3 306-316. 

Hemodynamics (blood pressure and heart rate), electrophysiology (EKG in dog and other such screens for QTc prolongation as appropriate), and autonomic function in response to a pharmacologic challenge... 

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