generally speaking , this invention is directed to a method of preventing and / or treating pah in an animal or human body . in particular the invention relates to the prevention and / or treatment of pulmonary arterial hypertension by administering a therapeutically effective amount of a compound that is both a 5 - ht 2a and 5 - ht 2b receptor antagonist to an animal including mammals in general and humans in particular , for the treatment or prevention and / or treatment of pulmonary arterial hypertension ( pah ). another aspect of the invention relates to administering at least two separate compounds one that is a 5 - ht 2a receptor antagonist and a second that is a 5 - ht 2b receptor antagonist for treating and / or preventing pulmonary arterial hypertension ( pah ) in animals including mammals , especially humans . iferanserin , s - 2 ′-[ 2 -( 1 - methyl - 2 - piperidyl ) ethyl ] cinnamanilide ( s - mpec ), disclosed in u . s . pat . no . 5 , 780 , 487 , is both a 5 - ht 2a and 5 - ht 2b receptor antagonist and can be administered to an animal , including mammals in general and humans in particular , for prevention and / or treatment of pulmonary arterial hypertension ( pah ). the method comprises administering to such an animal or mammal , especially humans , who has or is at risk of developing pah , an effective amount of a 5 - ht 2a and 5 - ht 2b receptor antagonist such as s - 2 ′-[ 2 -( 1 - methyl - 2 - piperidyl ) ethyl ] cinnamanilide ( s - mpec ) or a pharmaceutically acceptable acid salt thereof . s - 2 ′-[ 2 -( 1 - methyl - 2 - piperidyl ) ethyl ] cinnamanilide or its acid salt uniquely blocks both 5 - ht 2a and 5 - ht 2b receptors at a reasonable dose range . it is relatively safe , and with minimal activities on other receptors , consequently has minimal side effects . it is bio - available orally and has an acceptable half - life . as described below , the effects of s - 2 ′-[ 2 -( 1 - methyl - 2 - piperidyl ) ethyl ] cinnamanilide in acute hypoxia - induced pulmonary hypertension was measured and it was determined that iferanserin partially inhibited the acute hypoxia - induced pulmonary hypertension in adult rats . these results support the conclusion that s - 2 ′-[ 2 -( 1 - methyl - 2 - piperidyl ) ethyl ] cinnamanilide or a pharmaceutically acceptable salt thereof can be used for the treatment and / or prevention of pah . the combined 5 - ht 2a and 5 - ht 2b receptor antagonist ( s ) may be employed in free form or as a generally water soluble non - toxic pharmaceutically acceptable addition salt such as an basic or acidic addition salt such as for the acidic addition salt with such relatively non - toxic organic or inorganic acids as sulfuric , sulfonic , phosphoric , phosphonic , hydrobromic , hydrochloric , hydroriodic , sulfamic , methanesulfonic , benzenesulfonic , para - toluenesulfonic , acetic , lactic , succinic , malic , mucic , tartaric , citric , gluconic , benzoic , cinnamic , isethionic and the like . the individual 5 - ht 2a and 5 - ht 2b receptor antagonists may also be employed in free form or as a generally water soluble non - toxic pharmaceutically acceptable acid or basic addition salt as described above . pharmaceutical compositions for use in the treatment or prevention of pah may in the forms normally employed and may be taken orally ; parenterally , by intravenous , subcutaneous , or intramuscular injection ; or by inhalation therapy ; or transdermally . when multiple 5 - ht receptor antagonists are used , they may be administered together , serially or in other ways such that the desired result is achieved . they may be administered by the same or different means and / or in the same or different suitable dosage forms . for example , the composition containing a combined 5 - ht 2a and 5 - ht 2b receptor antagonist ( s ) or a pharmaceutically acceptable acid salt thereof , may be prepared and used in any suitable solid or liquid form , e . g . powder , paste , tablet , capsule , lozenge , gel , chewing gum , solution , suspension , emulsion , aerosol , syrup , elixir , aqueous or oily suspension , emulsion or solution or aerosol . suitably the compositions of this invention comprise sufficient active material ( s ) to provide a dose of from 0 . 05 - 100 mg . per kg . of body weight , more suitably 0 . 2 - 60 mg / kg body weight . these compositions may be taken 1 - 3 times daily or as needed until the symptom or condition being treated subsides or is corrected . actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient , which is effective to achieve the desired therapeutic response for a particular patient , composition , and mode of administration without being toxic or resulting in unacceptable side effects to the patient . these compositions may contain the active ingredient in amounts ranging from less than 1 % to over 99 %, with the remainder being a pharmaceutically acceptable solid or liquid carrier , which may contain other conventional excipients . by “ pharmaceutically acceptable ” it is meant the carrier , diluent , excipient , and / or salt must be compatible with the other ingredients of the formulation , and not deleterious to the recipient thereof . examples of such carriers and excipients include fillers , binders , flavors , sweeteners , bulking and coloring agents , antioxidants , anionic , nonionic , cationic , zwitterionic , and amphoteric surface active detergents , sudsing , dispersing and emulsifying agents , buffering and ph adjusting agents , water and organic solvents , humectants , thickeners , preservatives , stabilizers , mold release agents , disintegrants , anti - disintegrants , lubricants and the like . examples of conventional pharmaceutically acceptable carriers and excipients are profusely disclosed in the prior art including discussions in u . s . pat . no . 4 , 515 , 772 ( parran et al , proctor & amp ; gamble ), u . s . pat . no . 4 , 966 , 777 ( gaffar et al , colgate - palmolive company ), and u . s . pat . no . 4 , 728 , 512 ( mehta et al , american home products ), which discussions are incorporated herein by reference thereto . the following example is only illustrative of certain preferred embodiments of this invention . all parts and proportions referred to herein and in the appended claims are by weight and temperatures are in degrees centigrade , unless otherwise indicated . male sprague - dawley rats were obtained from charles river breeding laboratories ( wilmington , mass .) at 9 - 10 wk of age . for pulmonary arterial pressure measurement , a closed - chest technique ( 1 - 4 ). under ketamine ( 80 mg / kg ) and xylazine ( 5 mg / kg ) anesthesia , a small transverse cut was made in the proximal right external jugular vein through passed . the introducer was a blunted 7 . 5 cm , 19 - gauge needle with the tip turned up 30 degrees . the silastic catheter filled with heparinsaline solution was passed through the introducer and attached by a 25 gauge blunted needle to a pressure transducer ( model cp - 01 , century technology , inglewood , calif .) coupled to a polygraph ( model 7 , grass instruments , quincy , mass .). after the introducer was placed in the right ventricular cavity , the tip was directed anteriorly . the catheter was then advanced into the pulmonary artery . catheter position was identified by the pressure tracing . the introducer was slipped out over the catheter and removed after a typical pulmonary arterial pressure tracing was recorded . the catheter was affixed to the vein and to the surrounding tissue distally by basketweave sutures and connected to polyethylene tubing ( pe - 10 fused to pe - 20 ) with a loop . the pe - 20 tubing was exteriorized at the back of the neck by a stainless steel wire ( 0 . 018 in . diam .) tunneled subcutaneously . for systemic arterial pressure measurement , an arterial cannula ( pe - 10 fused to pe - 50 ) was inserted into the femoral artery , advanced into the dorsal aorta , and the pe - 50 tubing was also exteriorized at the back of the neck . one day after catheterization , mean pulmonary arterial pressure ( mpap ), mean systemic arterial pressure ( msap ) were recorded through the pulmonary and femora arterial catheters via transducers coupled to the polygraph . on the day of the testing of rat &# 39 ; s response to acute hypoxic exposure , after stable msap and mpap recordings were obtained from the conscious unrestrained rats , iferanserin ( 3 and 10 mg / kg , dissolved in 0 . 9 % saline at ph 5 . 5 , or 3 % gum arabic ) or vehicle was administered orally 45 min before exposure to normobaric hypoxia ( 10 % o 2 , 1 atm ). rats were maintained in hypoxia for 90 min and then returned to normoxia ( room air ) for 15 min before the termination of mpap and msap measurement . rats were exposed to hypoxia in a 330 - liter plexiglas glove box ( manostat , brookyln , n . y .) ( 1 - 4 ). hypoxic exposures ( range 10 . 0 + 0 . 5 % o 2 ) were accomplished by intermittently adding n 2 ( southern welding , birmingham , ala .) to the chamber from a liquid n 2 reservoir , the gas outflow of which was regulated by a solenoid valve controlled by the recorder output of an s3 - a o2 analyzer ( applied electrochemistry , sunnyvale , calif .) through a control circuit ( model 371 - k , lfe , clinton , mass .). a baralyme co 2 scrubber ( allied health care products , st . louis , mo .) kept the co 2 concentration at & lt ; 0 . 2 %. relative humidity within the chamber was kept at & lt ; 70 % with anhydrous caso 4 . boric acid was used to keep nh 3 levels within the chamber at a minimum . animals were permitted to have standard laboratory chow and tap water ad libitum . iferanserin partially inhibited the acute hypoxia - induced pulmonary hypertension in adult rats . there were no dose - dependent response within the range of 3 - 10 mg / kg , p . o . this invention has been disclosed with respect to certain preferred embodiments , and it will be understood that modifications and variations thereof obvious to those skilled in the art are to be included within the spirit and purview of this application and the scope of the appended claims . 1 . oparil s , chen s j , meng q c , elton t s , yano m , chen y f . endothelin - a receptor antagonist prevents acute hypoxia induced pulmonary hypertension in the rat . am j physiol 1995 ; 268 : l95 - l100 . 2 . li h , oparil s ., meng o c , elton t s , chen y f , selective down - regulation of anp clearance receptor gene expression in lung of rats adapted to hypoxia . am j physiol 199 ; 268 : l328 - l335 . 3 . chen s j , chen y f , meng q c , durand j . dicarlo v s , oparil s . endothelin receptor anatagonist bosentan prevents and reverses hypoxia induced pulmonary hypertension in rats . j appl physiol 1995 ; 79 : 2122 - 2131 . 4 . tilton r g , munsch c l , sherwood s j , chen y f , wuc , brock n . dixon r a , brock t a . attenuation of pulmonary vascular hypertension and cardiac hypertrophy with sitaxsentan , an orally et ( a ) receptor antagonist . pul pharmacol ther 2000 ; 13 : 87 - 97 .
pulmonary arterial hypertension in a mammal can be prevented or treated using combined 5 - ht2a and 5 - ht2b receptor antagonist . the antagonists can be present in a single compound or in two separate compounds