Table 1.

Models for study of MC compounds on Penile Erection

Model	Comment
In vitro
Cell culture	Determine MC receptor affinities, activation/inhibition of cAMP production in cells expressing specific MC receptors Determine, in cavernosal smooth muscle cells, calcium responses to specific MC agonists
Organ bath	• Measure corpus cavernosal (end organ) relaxation in response to direct drug application
In vivo
Animal studies
Spontaneous erections	• Site specific drug delivery: intracerebral, intrathecal, intracavernosal or systemically followed by observation period. May or may not mimic behaviorally stimulated erection. Observer dependent results
Mating behaviors	• Site-specific delivery as above. Place trained male in contact with trained receptive female in artificial estrous or separated by barrier (non-contact erections). Measure specific aspects of erection: mounts, intromissions, ejaculations, etc
Reflexogenic erections	• Site-specific delivery in a restrained or anesthetized animal. Monitor specific penile responses (cups, flares, flips) or intracorporal pressure respectively
Nerve stimulation studies	• Site-specific drug delivery with nerve stimulation (usually cavernous nerve) in an anesthetized animal. Evaluation for facilitation or inhibition of erection by drug
Human studies
Laboratory based	• Drug delivery IV, SQ or intranasal. Monitor penile tumescence w/ Rigi-scan with or without visual sexual stimulation. (VSS)
At home trials	• Phase II and III trials to determine safety, pharmacokinetics and efficacy using validated self report questionnaires and event diaries