**2.5 Papaverine**

IUPAC name: 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline


Papaverine, which has no opioid-like effect, is the fifth opioid alkaloid based on its density in the raw *Papaver somniferum L.* plant, first isolated from opium by Merck in 1848. Papaverine affects the heart muscle and vascular smooth muscle by blocking non-selective phosphodiesterase and calcium channels [92]. Papaverine suppresses conduction and prolongs the refractory period in the heart. Vasodilatation occurs with direct effect on vascular smooth muscles including coronary and pulmonary arteries. Papaverine-mediated relaxation in smooth muscles is independent of muscle innervation and therefore does not cause paralysis in the muscles. Papaverine-mediated these effects are more pronounced especially in ischemia with arteriospasm [93]. Papaverine is used in the treatment of myocardial infarction, angina, peripheral and pulmonary embolism, peripheral vascular disease, cerebral angiospastic states. It can also be used in hypertension, urinary incontinence, prostate hyperplasia and erectile dysfunction [94]. Papaverine also has antiviral activity, which is particularly pronounced against respiratory syncytial virus, cytomegalovirus and HIV [95]. Papaverine is taken orally, intramuscularly, intravenously, and intra-arterially.

Absorption is nearly total in oral use. Oral bioavailability is higher due to less first-pass metabolism (about 54%). Papaverine is distributed to a variety of tissues, with priority being to the adipose tissue and liver. 6-Desmethylpapaverine (6-DMP, major metabolite) and 4<sup>0</sup> ,6-didesmethylpapaverine (4,6-DDMP) is formed as a result of hepatic metabolism [96]. Half-life elimination is 0.5–2 h. The excretion of papaverine is through primarily urine [97]. No information on toxic blood concentrations is available. The oral median lethal dose in rats is 360 mg/kg, unknown in humans [98].
